Methods of providing frozen compositions and devices therefor

Abstract

The present disclosure relates to a method for providing a frozen composition and an apparatus therefor, and more particularly, to a method for spraying a composition in a frozen state to a target area and an apparatus therefor. The liquid composition is sprayed with a coolant, and the composition can reach a target area by freezing to a solid state by means of a refrigerant having a relatively low temperature. The solid composition has improved skin permeability compared to the liquid composition.

Description

Technical Field

[0001] This disclosure generally relates to a method and apparatus for providing a frozen composition, and more specifically, to a method and apparatus for spraying a frozen composition onto a target area. Background Technology

[0002] Regarding the delivery of compositions to the skin, the extent to which the composition penetrates the skin has a significant impact on the degree of effect produced by the composition. Therefore, various studies have been conducted to improve the ability of compositions to penetrate the skin.

[0003] Methods of delivering a composition to the skin include applying the composition to the skin, injecting the composition into the skin, or spraying the composition onto the skin.

[0004] It is known that, depending on the molecular weight and biochemical properties of the composition, applying the composition to the skin makes it difficult for the composition to penetrate the lipid layer of the skin, and therefore only a very small amount is absorbed into the skin.

[0005] Furthermore, injecting the composition into the skin allows it to penetrate deep into the skin, but inevitably damages the skin. This can cause not only pain during the procedure but also problems such as bruising or swelling due to skin damage. In addition, injecting the composition into the skin requires skill from the operator; therefore, depending on the operator, the depth and amount of penetration may vary. This is disadvantageous because the effects of the composition may be inconsistent.

[0006] Therefore, there is a need for a composition delivery method that ensures the ability of the composition to penetrate the skin and produce a consistent penetration effect while minimizing damage to the skin. Summary of the Invention

[0007] Technical issues

[0008] One objective is to enable the composition to reach a depth below the skin's epidermis.

[0009] Another objective is to enable the composition to reach depths below the stratum corneum of the skin.

[0010] Another objective is to enable the composition to reach the dermis layer of the skin.

[0011] Another objective is to freeze the composition, which is liquid at room temperature, and then apply the composition to the skin in a solid state.

[0012] Another objective is to spray the composition onto the skin, wherein the freezing ratio of the composition reaching the skin is equal to or greater than a predetermined value.

[0013] Another objective is to freeze the composition into particles equal to or smaller than a predetermined size and to deliver the frozen composition to the skin.

[0014] Another objective is to deliver the cryogenic composition to the skin at a rate equal to or greater than the predetermined rate.

[0015] Another objective is to provide a composition that simultaneously maintains skin temperature at a predetermined value or within a predetermined range.

[0016] The purpose of this disclosure is not limited to those mentioned above, and other purposes not mentioned will be clearly understood by those skilled in the art from the following description and drawings.

[0017] Problem-solving methods

[0018] According to one embodiment, a method for freezing and spraying a composition is provided, the method comprising: preparing a mixing spraying system configured to spray a refrigerant and a composition, the mixing spraying system including a nozzle configured to spray the refrigerant and a composition guide arranged adjacent to the nozzle; positioning the mixing spraying system at a distance from a target area, wherein the orifice of the nozzle of the mixing spraying system is an outlet for spraying the refrigerant, and the orifice is positioned toward the target area; and spraying the composition containing the refrigerant onto the target area using the mixing spraying system, the nozzle forming a refrigerant spray stream, and the composition... A guide leads a liquid composition into a refrigerant spray stream, and a portion of the liquid composition is frozen and reaches the target area as a solid composition; wherein, at a point in time during the spraying of the refrigerant and composition through the mixing spraying system, the freezing ratio representing the solid composition to the liquid composition and the solid composition in the observation area is greater than or equal to 5%, wherein the observation area is defined as an area of ​​arbitrary width at a certain observation distance from the nozzle orifice in a side view of the mixing spraying system, and wherein the observation distance corresponds to the distance between the nozzle orifice and the target area.

[0019] According to one embodiment, a cryogenic spraying system for freezing and spraying compositions is provided, the cryogenic spraying system comprising: a refrigerant container in which refrigerant is stored at a pressure between 10 bar and 1000 bar; a refrigerant receiving unit configured to receive refrigerant from the refrigerant container; a nozzle having an orifice of a predetermined size and configured to spray refrigerant, the nozzle pressurizing the refrigerant passing through it such that the refrigerant encounters atmospheric pressure and expands, thereby lowering the temperature of the refrigerant; a composition container containing a composition; and a composition guide fluidly connected to the composition container and configured to allow the composition to... The composition is discharged, and the end of the composition guide is arranged adjacent to the nozzle so that the composition is introduced into the refrigerant flow sprayed by the nozzle; a valve is disposed between the refrigerant receiving unit and the nozzle and is configured to control the flow rate of refrigerant from the refrigerant receiving unit to the nozzle; and a controller is configured to control the valve, wherein when the refrigerant and the composition are sprayed from the cryogenic spraying system, the freezing ratio, representing the ratio of the composition in a solid state to the composition in a liquid state at a point in time in the observation area, is greater than or equal to 5%, and wherein the observation area is positioned at a certain observation distance from the orifice of the nozzle and has an arbitrary width.

[0020] The means of solving this problem are not limited to those mentioned above, and those skilled in the art can clearly understand from this specification and the accompanying drawings any solutions not mentioned.

[0021] Effects of the present invention

[0022] According to one embodiment, the composition can reach a depth below the skin epidermis.

[0023] According to one embodiment, the composition can reach a depth below the stratum corneum of the skin.

[0024] According to another embodiment, the freezing composition can be made to reach the skin surface.

[0025] According to another embodiment, the degree of freezing of the composition reaching the skin surface can be controlled.

[0026] According to another embodiment, the amount of composition penetrating into the skin can be increased compared to the amount of composition provided to the skin surface.

[0027] The effects of this disclosure are not limited to those mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the following description and drawings. Attached Figure Description

[0028] Figure 1 To illustrate a schematic diagram of a hybrid spraying system according to one embodiment;

[0029] Figure 2 A view illustrating how the composition is frozen and sprayed according to one embodiment;

[0030] Figure 3 A view illustrating how the observation area is used to determine the freezing ratio of the composition according to one embodiment;

[0031] Figure 4 and Figure 5 Images of a scene where a liquid composition and a solid composition are sprayed according to one embodiment;

[0032] Figure 6 A view illustrating an image processing procedure for statistical analysis of solid composition particles according to one embodiment;

[0033] Figure 7 A view illustrating how the freezing ratio is calculated using observation lines according to one implementation scheme;

[0034] Figure 8 A view showing a hybrid spraying system according to one embodiment;

[0035] Figure 9 A view showing the components of a refrigerant spraying apparatus according to one embodiment;

[0036] Figure 10 A view showing a composition supply device according to one embodiment;

[0037] Figure 11 A view showing a composition supply device according to another embodiment;

[0038] Figure 12 A flowchart illustrating a cryogenic spraying method according to one embodiment;

[0039] Figure 13 and Figure 14 A view showing the results of a first experiment used to confirm the permeation effect depending on freezing and the permeation effect depending on the freezing ratio;

[0040] Figure 15 A view showing the results of a second experiment used to confirm the permeation effect depending on the freezing ratio;

[0041] Figure 16 A view showing the penetration effect of test group 1 and test group 5 in the second experiment;

[0042] Figure 17 A view illustrating the relationship between particle size and spraying speed according to one embodiment; and

[0043] Figure 18 A view showing the experimental results used to demonstrate the penetration effect depending on the skin surface temperature. Detailed Implementation

[0044] According to one embodiment, a method for freezing and spraying a composition is provided, the method comprising: preparing a mixing spraying system configured to spray a refrigerant and a composition, the mixing spraying system including a nozzle configured to spray the refrigerant and a composition guide arranged adjacent to the nozzle; positioning the mixing spraying system at a distance from a target area, wherein the orifice of the nozzle of the mixing spraying system is an outlet for spraying the refrigerant, and the orifice is positioned toward the target area; and spraying the composition containing the refrigerant onto the target area using the mixing spraying system, the nozzle forming a refrigerant spray stream, and the composition guide guiding the liquid. A bulk composition is introduced into a refrigerant spray stream, and a portion of the liquid composition is frozen and reaches the target area as a solid composition; wherein, at a point in time during the spraying of the refrigerant and composition through the mixing spraying system, the freezing ratio representing the solid composition to the liquid and solid compositions in the observation area is greater than or equal to 5%, wherein the observation area is defined as an area of ​​arbitrary width at a certain observation distance from the nozzle orifice in a side view of the mixing spraying system, and wherein the observation distance corresponds to the distance between the nozzle orifice and the target area.

[0045] In the side view of the hybrid spraying system, the observation area is defined by a first line and a second line. The first line is a certain observation distance away from the nozzle orifice and is perpendicular to the central axis of the nozzle. The second line is any width away from the first line and is parallel to the first line.

[0046] The observation distance is within the recommended spraying distance range determined for the hybrid spraying system.

[0047] At a given time point in the observation area, the freezing ratio is the ratio of the number of particles in the solid state of the composition to the sum of the number of particles in the liquid state and the number of particles in the solid state of the composition.

[0048] The freezing ratio is 17% or higher.

[0049] The velocity of the solid composition reaching the target area is 50 m / s or greater.

[0050] The average size of the composition in solid state present in the observation area is 20 μm to 60 μm.

[0051] According to one embodiment, a cryogenic spraying system for freezing and spraying compositions is provided, the cryogenic spraying system comprising: a refrigerant container in which refrigerant is stored at a pressure between 10 bar and 1000 bar; a refrigerant receiving unit configured to receive refrigerant from the refrigerant container; a nozzle having an orifice of a predetermined size and configured to spray refrigerant, the nozzle pressurizing the refrigerant passing through it such that the refrigerant encounters atmospheric pressure and expands, thereby lowering the temperature of the refrigerant; a composition container containing a composition; and a composition guide fluidly connected to the composition container and configured to... The composition is discharged, and the end of the composition guide is arranged adjacent to the nozzle so that the composition is introduced into the refrigerant flow sprayed by the nozzle; a valve is disposed between the refrigerant receiving unit and the nozzle and is configured to control the flow rate of refrigerant from the refrigerant receiving unit to the nozzle; and a controller is configured to control the valve, wherein when the refrigerant and the composition are sprayed from the cryogenic spraying system, the freezing ratio, representing the ratio of the solid state composition to the liquid state composition at a point in time in the observation area, is greater than or equal to 5%, and wherein the observation area is positioned at a certain observation distance from the orifice of the nozzle and has an arbitrary width.

[0052] In the side view of the cryogenic spraying system, the observation area is defined by a first line and a second line. The first line is a certain observation distance away from the nozzle orifice and is perpendicular to the central axis of the nozzle. The second line is any width away from the first line and is parallel to the first line.

[0053] The observation distance is within the recommended spraying distance range determined for the hybrid spraying system.

[0054] The cryogenic spraying system also includes a heating unit disposed between the refrigerant receiving unit and the nozzle and configured to heat at least a portion of the refrigerant moving from the refrigerant receiving unit to the nozzle; wherein, by using the heating unit, the controller is configured to heat the refrigerant such that the freezing ratio becomes 5% or greater.

[0055] The controller is configured to apply electrical power within a predetermined range to the heating unit, wherein the heating unit is applied electrical power and generates heat energy transferred to the refrigerant, and wherein the predetermined electrical power range is set such that the refrigeration ratio becomes 5% or greater.

[0056] At a given time point in the observation area, the freezing ratio is the ratio of the number of particles in the solid state of the composition to the sum of the number of particles in the liquid state and the number of particles in the solid state of the composition.

[0057] The cryogenic spraying system also includes an actuator coupled to the composition container and configured to supply the composition to the composition guide.

[0058] The composition guide includes an input end for the composition to flow in and an output end for the composition to discharge out, wherein the output end of the composition guide is positioned at a predetermined distance from the nozzle end.

[0059] The purposes, features, and advantages of this disclosure described above will become clearer from the following detailed description when taken in conjunction with the accompanying drawings. However, this disclosure may be embodied in many different forms and should not be limited to exemplary embodiments. In the hereinafter, reference will be made to embodiments in more detail, specific examples of which are shown in the accompanying drawings.

[0060] In the accompanying drawings, the thickness of layers and regions is exaggerated for clarity. Furthermore, when an element or layer is referred to as "above" or "on top of" another element or layer, it may be directly above the other element or layer, or there may be intermediate elements or layers between them. In principle, throughout the specification, the same reference numerals denote the same elements. Additionally, the same reference numerals are used to denote elements that have the same function within the same concept shown in the drawings of each embodiment, and descriptions of overlap will be omitted.

[0061] The numbers used in this description (e.g., first, second, etc.) are merely identifiers used to distinguish one element from another.

[0062] In addition, the component suffixes “module” and “section” used in the following embodiments are given or used in combination only for the convenience of writing the specification, and they do not have any meaning or function that distinguishes them from each other.

[0063] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein are intended to include the plural forms as well.

[0064] In the following implementations, when used in this specification, terms such as “comprising,” “including,” and “having” specify the presence of the said feature or element, but do not exclude the presence or addition of one or more other features or elements.

[0065] In the accompanying drawings, the dimensions of the elements may be exaggerated or reduced for ease of explanation. For example, the dimensions and thicknesses of the elements in the drawings are arbitrarily shown for ease of explanation, and the embodiments of this disclosure are not limited thereto.

[0066] The specific process steps described herein may be performed in other ways when some exemplary embodiments may be embodied in other ways. That is, for example, two process steps described in sequence may be performed at approximately the same time or in reverse order.

[0067] In the following implementation, when membranes, regions, elements, etc. are referred to as being connected to each other, they may be directly connected or indirectly connected to each other through one or more intermediate membranes, regions, elements, etc. inserted therebetween.

[0068] For example, when membranes, regions, elements, etc. are referred to as being electrically connected to each other, they can be directly electrically connected or indirectly electrically connected to each other through one or more intermediate membranes, regions, elements, etc. inserted therein.

[0069] In the following implementation, when membranes, regions, elements, etc. are referred to as being fluidly connected to each other, it can be understood that they may form at least a portion of the flow path through which each fluid flows.

[0070] For example, fluid connection between component A and component B might mean that fluid flowing through a flow path formed by component A can reach a flow path formed by component B, and vice versa. Specifically, when component A and component B are connected and the flow paths formed by component A and component B are directly connected to each other, component A and component B can be considered fluidly connected. In other cases, when component A and component B are connected to each other via component C (such as a pipe), such that the flow paths formed by component A and component B are indirectly connected to each other via a flow path formed by component C, component A and component B can be considered fluidly connected. Here, component C can be understood as fluidly connecting component A and component B. Furthermore, component A and component B can be fluidly connected to each other through multiple components.

[0071] Unless otherwise stated or apparent from the context, as used herein, the term “about” with respect to numbers or ranges of numbers is understood to mean the number stated and numbers plus or minus 10%, or for a range of values ​​listed, 10% below the listed lower limit and 10% above the listed upper limit.

[0072] This disclosure generally relates to a method and apparatus for providing a frozen composition, and more specifically, to a freeze spraying method and apparatus for spraying a frozen composition onto a target area.

[0073] The composition may include active substances that induce or produce medical effects. Alternatively, the composition may include active substances that induce or produce cosmetic effects.

[0074] Furthermore, the compositions in this disclosure are particularly characterized by transdermal delivery, and the compositions may refer to substances that produce cosmetic or medical effects during transdermal delivery.

[0075] The composition may include, for example, minerals, nucleic acids, amino acids, coenzymes, vitamins, nicotinamide, oil-soluble licorice extract, arbutin, hyaluronic acid, potassium hyaluronic acid, hydrolyzed hyaluronic acid, hydrolyzed sodium hyaluronic acid, hydroxypropyltrimethylammonium hyaluronic acid, acetylated sodium hyaluronic acid, sodium hyaluronic acid crosspolymer, sodium hyaluronic acid, retinol, retinyl palmitate, adenosine, peptides, coenzyme Q10, adult stem cells, antioxidants, poly-d-lactic acid (PDLA), polynucleotides, polydeoxyribonucleotides (PDRN), poly-d,l-lactic acid (PDLLA), lidocaine, botulinum toxin, exosomes, promecaine, tetracaine, human growth hormone, growth factors, cell therapy products, or combinations thereof.

[0076] In addition, the composition may also include: base ingredients such as purified water, glycerin, butylene glycol, propylene glycol and silicone oil; formulation-forming ingredients such as emulsifiers, surfactants and viscosity modifiers; and preservative ingredients such as parabens, phenoxyethanol, benzoic acid, triclosan, benzyl alcohol, methylisothiazolinone and 1,2-hexanediol.

[0077] In this disclosure, a delivery medium is used as a method for spraying the composition. For example, the composition can be carried by a refrigerant sprayed at a relatively high speed and sprayed onto the target area. In this case, the temperature of the composition can be reduced due to the refrigerant being sprayed at a relatively low temperature.

[0078] Here, the refrigerant can be liquefied carbon dioxide (CO2), carbon dioxide, liquefied nitrogen, liquefied oxygen, nitrogen dioxide (NO2), nitric oxide (NO), nitrous oxide (N2O), hydrofluorocarbon (HFC) materials, methane (CH4), perfluorocarbon (PFC), sulfur hexafluoride (SF6), or combinations thereof, and materials capable of applying cooling energy to the target area, such as refrigerants and cooling gases, can be used. In addition to refrigerants, compressed air can also be used.

[0079] In the following description, for ease of explanation, the composition will be described as being carried by a refrigerant and using liquefied carbon dioxide as the refrigerant, but the technical concept of this disclosure is not limited thereto.

[0080] A cryogenic composition refers to a composition in a liquid or gaseous state that transforms into a solid state as its temperature decreases. When the temperature of the composition decreases, it transforms into a solid composition having crystals. The cryogenic spraying method described in this disclosure can be understood as a method of freezing and spraying a liquid composition so that a solid composition is sprayed onto a target area.

[0081] In this disclosure, the target area refers to the area to which the composition is to be sprayed. Specifically, the target area may refer to a portion of the skin surface of a human body. Alternatively, the target area may refer to a portion of the skin surface of an animal other than a human. The target area may be determined depending on the body part to which the composition is to be provided.

[0082] The cryogenic spraying method described in this disclosure has several usage examples as follows.

[0083] Cryo-spraying can be used as a treatment method or medical procedure. Here, "composition" refers to a pharmaceutical or medicament and can be understood to include substances used for the diagnosis, cure, relief, treatment, or prevention of diseases or disorders, skin regeneration, lifting, and treatment of problems such as acne and inflammation.

[0084] Doctors and others (medical personnel and those with medical expertise as defined in the medical laws of each country) may use cryo-spraying to apply compositions that are effective against specific disorders or diseases to individuals in need of treatment.

[0085] Cryo-spraying can be used as a cosmetic method, procedure, or skincare treatment. Here, "composition" refers to a cosmetic product and can be understood to include substances that, when applied to the skin, produce cosmetic effects such as whitening, skin soothing, nourishing, moisturizing, wrinkle reduction, or elasticity enhancement. Furthermore, the composition may also consist of substances that have little or no effect on the human body.

[0086] Estheticians or skin care professionals can use a cryo-spray method to apply a cosmetically effective composition to the person being treated.

[0087] Cryo-spraying can also be used as a treatment or cosmetic procedure for animals other than humans. Here, "composition" refers to a pharmaceutical, medicament, or cosmetic product and can be understood to include active substances having therapeutic or cosmetic effects.

[0088] 1. Regarding the permeation of the composition

[0089] The primary purpose of the cryo-spraying method described in this disclosure is to allow the composition to penetrate the skin.

[0090] 1.1 Significance and Importance of Composition Penetration

[0091] The penetration of a composition refers to the depth to which the composition reaches from the skin surface. More specifically, the penetration of a composition refers to the depth to which the composition reaches below the epidermis.

[0092] The epidermis consists of the stratum corneum, stratum lucidum, stratum microsphere, stratum spinosum, and stratum basale. In particular, the stratum corneum acts as a skin barrier and is the main factor hindering the absorption of the composition.

[0093] Therefore, the penetration of a composition means that the composition reaches at least below the stratum corneum. Since the thickness of the stratum corneum is from about 10 μm to about 20 μm, the penetration of a composition means that the composition reaches a depth of about equal to or greater than 0.01 mm from the skin surface.

[0094] For example, when the composition is provided for the face of a Korean adult, the epidermis is distributed to a depth of about 0.1 mm from the skin surface, while the dermis is distributed to a depth of about 0.1 mm to about 2 mm from the skin surface.

[0095] The penetration of the composition into the face refers to the depth of the composition from the skin surface to a depth of about 0.01 mm to about 2 mm, about 0.02 mm to about 2 mm, about 0.1 mm to about 2 mm, about 0.2 mm to about 2 mm, about 0.3 mm to about 2 mm, about 0.4 mm to about 2 mm, about 0.5 mm to about 2 mm, about 0.6 mm to about 2 mm, about 0.7 mm to about 2 mm, about 0.8 mm to about 2 mm, about 0.9 mm to about 2 mm, about 1 mm to about 2 mm, about 1.1 mm to about 2 mm, about 1.2 mm to about 2 mm, about 1.3 mm to about 2 mm, about 1.4 mm to about 2 mm, about 1.5 mm to about 2 mm, about 1.6 mm to about 2 mm, about 1.7 mm to about 2 mm, about 1.8 mm to about 2 mm, or about 1.9 mm to about 2 mm. Because the thickness of the epidermis and dermis can vary depending on the area in the face, the reference depth for defining the penetration of the composition is not limited to the values ​​described above.

[0096] Furthermore, the target of the composition spraying is not limited to the face; other body parts besides the face (such as the scalp, neck, arms, legs, hands, and feet) can also be targeted. Here, the penetration of the composition also refers to the composition reaching the stratum corneum or below the epidermis of various parts of the body.

[0097] For a composition to achieve its intended purpose (e.g., to produce a therapeutic or cosmetic effect), its absorption by the skin is essential. For a composition to be absorbed, it needs to reach and penetrate the stratum corneum to diffuse into the basal layer or dermis. In other words, even if a composition contains highly potent active ingredients, its effectiveness will inevitably be minimal when it remains in the stratum corneum.

[0098] There are three main pathways that enable the composition to penetrate the epidermis into the dermis. These include: a transcellular pathway that directly penetrates the stratum corneum of the epidermis, an intercellular pathway that penetrates the nonpolar lipid layer between keratinocytes, and a trans-appendage pathway that penetrates appendages such as pores.

[0099] However, since appendages occupy only 0.1% of the skin surface area, the amount of permeation through them is limited. Therefore, permeation via transcellular or intercellular pathways is more important than permeation through appendages.

[0100] 1.2 Conventional Composition Permeation Methods and Problems

[0101] Conventional methods for penetrating a composition into the skin include applying the composition, injecting the composition using a syringe, puncturing the skin with microneedles after applying the composition, and spraying the composition in the form of microparticles.

[0102] Applying the composition to the skin surface via a topical method aims to allow the composition to penetrate via transcellular or intercellular pathways. However, even when the applied composition crosses the stratum corneum via a transcellular pathway, it is blocked by the microparticle layer of the epidermis, making it difficult to penetrate the stratum spinosum or stratum basale, and consequently, the composition has difficulty reaching the dermis. Even when the composition crosses the stratum corneum via an intercellular pathway, the amount that passes through is extremely small, resulting in insufficient composition reaching the dermis.

[0103] Injection using a syringe involves invasively delivering the composition by inserting a syringe into the dermis or subcutaneous tissue. Compared to other penetration methods, injection using a syringe is associated with relatively intense pain, and the composition tends to be concentrated at a single point in the skin rather than spreading evenly. Furthermore, the location of the composition introduced into the skin varies depending on the depth of insertion. Since the total thickness of the epidermis and dermis is approximately 2 mm, the accuracy of syringe insertion into the dermis depends heavily on the operator's skill level, and therefore, consistent treatment outcomes may not be guaranteed.

[0104] The acupuncture method includes: applying the composition to the skin, using an acupuncture device equipped with multiple microneedles of micron-scale length to form pores in the skin, and allowing the composition to penetrate through the pores.

[0105] In the case of acupuncture, microneedles are inserted into the skin to which the composition has been applied, or the composition penetrates into the skin through pores formed by the microneedles. Due to the thickness of the microneedles, the pores formed in the skin are also relatively small; therefore, the amount of composition introduced through the pores is limited.

[0106] Additionally, depending on the needle size of the acupuncture device, acupuncture may be painful, and the skin can be damaged when the device creates a hole. Therefore, extra care is needed to repair skin damage after the composition has penetrated. Furthermore, sterilization before use is crucial to prevent infection from the needle.

[0107] The airbrush method uses compressed air as a delivery medium and a fine nozzle (1500) to atomize the composition into relatively fine particles and spray it onto the skin. The airbrush method is a non-invasive, painless, and easy-to-use method for delivering the composition. However, in the airbrush method, the composition, in liquid form, impacts the skin surface, making it difficult to generate an impact force strong enough to physically pierce the epidermis. Therefore, in the airbrush method, the composition passes through the stratum corneum via transcellular or intercellular pathways, but like the smear method, it is difficult for the composition to penetrate the stratum spinosum or stratum basale of the epidermis.

[0108] 1.3 Delivery method of composition using refrigerant

[0109] As a method for penetrating the composition into the skin, this disclosure will describe a method using a hybrid spraying system 100.

[0110] Figure 1 A schematic diagram of a hybrid spraying system 100 according to one embodiment is shown.

[0111] The hybrid spraying system 100 employs a method of spraying a composition using a refrigerant. (Reference) Figure 1 The mixed spraying system 100 may include a refrigerant spraying device 1000 and a composition supply device 2000.

[0112] The refrigerant spraying apparatus 1000 refers to an apparatus for spraying refrigerant. The refrigerant spraying apparatus 1000 includes at least a refrigerant container RC in which the refrigerant is stored; a flow regulating unit 1200 that controls the movement of the refrigerant, causing the refrigerant to be sprayed from or not from the refrigerant spraying apparatus 1000; and a nozzle 1500 through which the refrigerant is sprayed. In addition to the components described above, the refrigerant spraying apparatus 1000 may further include other components necessary for operation. These additional components of the refrigerant spraying apparatus 1000 will be described later.

[0113] The composition supply device 2000 refers to a device for supplying a composition. The composition supply device 2000 may include a composition container CC for storing the composition and a composition guide 2100 for discharging the composition. The composition guide 2100 may include an input end and an output end, through which the composition stored in the composition container CC is introduced and the composition is discharged through the output end. In addition to the components described above, the composition supply device 2000 may further include other components necessary for operation. These additional components of the composition supply device 2000 will be described later.

[0114] The composition supply device 2000 can be connected to the refrigerant spraying device 1000 and supply composition to the refrigerant sprayed from the refrigerant spraying device 1000. Specifically, the nozzle 1500 of the refrigerant spraying device 1000 can form a refrigerant spray stream, and the composition guide 2100 of the composition supply device 2000 can be arranged adjacent to the nozzle 1500.

[0115] Here, the refrigerant spray stream refers to a refrigerant stream comprising refrigerant particles sprayed from nozzle 1500. The refrigerant spray stream formed by nozzle 1500 can create a negative pressure at the output end of composition guide 2100, and this negative pressure can allow the composition to move along composition guide 2100 and be introduced into the refrigerant spray stream. Alternatively, composition supply device 2000 may include actuator 2200 fluidly connected to composition container CC. The composition can be supplied to composition guide 2100 and introduced into the refrigerant spray stream via actuator 2200 at a predetermined flow rate or within a predetermined range.

[0116] The composition introduced into the refrigerant spray stream can collide with the refrigerant particles in the refrigerant spray stream and be sprayed together. The composition in the refrigerant spray stream can be broken into fine particles by the high-speed refrigerant spray stream and cooled by heat exchange with the refrigerant spray stream which has a relatively low temperature. Thus, in the mixed spraying system 100, the composition and refrigerant can be mixed and sprayed.

[0117] Meanwhile, the internal pressure of the refrigerant container RC storing the refrigerant at room temperature can be from about 10 bar to about 1000 bar. Alternatively, the internal pressure of the refrigerant container RC at room temperature can be from about 30 bar to about 200 bar. Alternatively, the internal pressure of the refrigerant container RC at room temperature can be about 50 bar. The internal pressure of the refrigerant container RC may be related to the expansion rate of the refrigerant when it is discharged from the nozzle 1500 of the refrigerant spraying device 1000. In other words, as the internal pressure of the refrigerant container RC increases, the velocity of the refrigerant particles in the refrigerant spray stream may increase. Considering that the pressure of the compressed air used in the spray gun method described above is from about 1 bar to about 5 bar, using a high-pressure refrigerant as a transfer medium can significantly increase the spraying speed of the composition, thereby improving the penetration effect of the composition.

[0118] However, even after reviewing numerous existing documents, it remains unknown whether the composition can effectively penetrate the skin when the state of the composition upon reaching the skin surface is controlled using the mixing spray system 100. In particular, it remains unknown whether the composition can effectively penetrate the skin when it reaches the skin surface in a "frozen" state.

[0119] Existing experimental history has shown that spraying carbon dioxide along with the composition can reduce cellulite. However, this has been interpreted as not revealing that a significant amount of the composition "reaches" the fat cells due to the cooling effect of carbon dioxide, and therefore does not provide an indication of a relatively large amount of the composition penetrating into the skin.

[0120] During the development of the hybrid spraying system 100, the applicant conducted an experiment to determine the extent to which the composition penetrates the skin when sprayed together with a refrigerant, and confirmed that the composition of this method can effectively penetrate the skin compared to conventional methods. As a result of the investigation into the reasons for this, it was confirmed that the improved penetration effect is not simply due to the composition being sprayed together with a refrigerant, but rather because the composition is sprayed in a frozen state.

[0121] More specifically, in observing the process of the composition being sprayed together with the refrigerant in the mixed spraying system 100, the applicant confirmed that a portion of the composition, which was in a liquid state before spraying, was frozen by the refrigerant and impacted the skin surface in a solid state.

[0122] Figure 2 A view illustrating how the composition is frozen and sprayed according to one embodiment. Reference Figure 2 When the refrigerant spray stream RSS is formed by nozzle 1500, the composition is discharged in liquid state from composition guide 2100 and introduced into the refrigerant spray stream RSS. As the composition in liquid state is sprayed together with the refrigerant spray stream RSS, it transforms into solid frozen particles, and these frozen particles reach the skin surface.

[0123] The applicant hypothesizes that the fact that the composition is frozen by the refrigerant and becomes frozen particles is a factor that enhances the composition’s penetration ability, and as described below, the applicant has improved the hybrid spraying system 100 to perform cryogenic spraying and conducted cryogenic spraying experiments.

[0124] 2. A method for freezing and spraying the composition.

[0125] 2.1 About cryogenic spraying

[0126] Cryo-spraying refers to applying a frozen composition to the skin surface, resulting in a significant penetration effect.

[0127] Significant penetration effect means that the composition penetrates into the skin at a level equal to or higher than the predetermined level. Additionally, significant penetration effect means that the composition penetrates deep into the skin.

[0128] More specifically, a significant penetration effect refers to the amount of composition reaching below the skin epidermis, relative to the amount of composition sprayed, when the composition is frozen and sprayed onto the skin surface.

[0129] Alternatively, when the same amount of composition is mixed with refrigerant sprayed at the same rate and applied to the skin surface, the penetration effect is significant when the amount of the penetrating composition is greater than when it is applied to the skin surface in a non-frozen state.

[0130] Alternatively, significant penetration effect refers to at least a portion of the composition reaching below the skin epidermis when the composition is frozen and sprayed onto the skin surface.

[0131] When the composition is applied to the skin surface via cryo-spray, it is expected to penetrate the epidermis more easily. This is because when the composition is frozen and impacts the skin surface as a solid composition, the impact force is expected to be greater than that of a liquid composition.

[0132] Specifically, when liquid composition particles and solid composition particles with the same momentum (mass * velocity) collide with the skin surface, the solid composition particles with higher hardness have a greater impact force due to the shorter collision time, and therefore may be more likely to penetrate the stratum corneum.

[0133] Furthermore, because solid composition particles are crystalline solids, their impact area with the skin surface may be smaller than that of liquid composition particles. Therefore, solid composition particles have a greater impact force per unit area and may penetrate the stratum corneum more easily than liquid composition particles.

[0134] The fact that the cryogenic composition penetrates the stratum corneum can be understood as the cryogenic particles of the composition forming pores on the skin surface and penetrating into the basal layer of the epidermis or the dermis below. Because the cryogenic composition acts like a needle, the cryo-spray method can also be called ice needle therapy.

[0135] 2.3 Cryo-spraying with enhanced penetration effect

[0136] As mentioned above, cryo-spraying refers to applying a frozen composition to the skin surface, causing the composition to penetrate the skin significantly.

[0137] Meanwhile, the applicant conducted the cryogenic spraying experiment described below and confirmed that when the degree of freezing of the composition reached a predetermined level, the penetration effect of the composition was improved compared with the spraying effect when the composition was sprayed in a non-frozen state.

[0138] More specifically, it was confirmed whether the penetration of the composition was enhanced when the temperature of the refrigerant spray was adjusted to allow the composition to move in a frozen state until it reached the skin surface. Therefore, it was confirmed that the penetration effect of the composition was improved. The first experiment related to this will be described later.

[0139] In addition, it is necessary to demonstrate how the penetration effect of the composition varies depending on the degree of freezing of the composition upon reaching the skin surface. The applicant conducted experiments, along with a second experiment which will be described later, to demonstrate this; and prior to that, the applicant established objective criteria for the degree of freezing of the composition during cryogenic spraying.

[0140] Here, the method of calculating and evaluating the freezing ratio when viewing the mixing spray system 100 from the side (e.g., left or right) is used as a method to determine the degree of freezing of the composition. Here, viewing the mixing spray system 100 from the side refers to viewing the mixing spray system 100 from the left or right during normal operation. For example, Figure 4 The image shown is an image of the mixing spraying system 100 viewed from the right. The method for calculating the freezing ratio and the method for designing the mixing spraying system 100 to control the freezing ratio will be described later.

[0141] First, when viewed from the side, the mixed spraying system 100 performing cryogenic spraying with a cryogenic ratio of 17% (measurement error within 5%, approximately 12% to approximately 22%) exhibits a higher penetration effect than when the cryogenic ratio is essentially 0%. Therefore, when the composition is sprayed onto the skin surface at a cryogenic ratio of 17%, the penetration effect of the composition is significant, and spraying at the corresponding cryogenic ratio can be understood as cryogenic spraying.

[0142] Furthermore, when viewed from the side, the mixed spraying system 100 performing cryogenic spraying with a cryogenic ratio of 5% (measurement error within 1%, approximately 4% to approximately 6%) exhibits a higher penetration effect than when the cryogenic ratio is essentially 0%. Therefore, when the composition is sprayed onto the skin surface at a cryogenic ratio of 5%, the penetration effect of the composition is significant, and spraying at the corresponding cryogenic ratio can be understood as cryogenic spraying.

[0143] Furthermore, it was confirmed that the penetration effect of the composition increased with the increase of the freezing ratio of the composition reaching the skin surface. Specifically, the penetration effect increased in the following order: when the freezing ratio of the composition was 5% (within 1% measurement error, approximately 4% to approximately 6%) → when the freezing ratio of the composition was 17% (within 5% measurement error, approximately 12% to approximately 22%), when the freezing ratio of the composition was 48% (within 3% measurement error, approximately 45% to approximately 51%), when the freezing ratio of the composition was 71% (within 3% measurement error, approximately 68% to approximately 74%), and when the freezing ratio of the composition was 100% (within 1% measurement error, approximately 99% to approximately 100%).

[0144] In other words, when the penetration effect is improved at a freezing ratio of 5% for the composition, a high penetration effect can be achieved even when the freezing ratio of the composition is equal to or higher than 5%. Therefore, the freezing ratio of the composition can be adjusted from 5% to 100%. Alternatively, the freezing ratio of the composition can be adjusted from 5% to 17%. Alternatively, the freezing ratio of the composition can be adjusted from 5% to 48%. Alternatively, the freezing ratio of the composition can be adjusted from 5% to 71%.

[0145] Taking into account the measurement error range, the freezing ratio of the composition can be adjusted from 2% to 100%. Alternatively, the freezing ratio of the composition can be adjusted from 2% to 22%. Alternatively, the freezing ratio of the composition can be adjusted from 2% to 51%. Alternatively, the freezing ratio of the composition can be adjusted from 2% to 74%.

[0146] Simultaneously, it was confirmed that the penetration effect of the composition decreases when the skin surface is overcooled by the refrigerant or the composition during the process of increasing the freezing ratio of the composition. More specifically, even when the freezing ratio of the composition reaching the skin surface is high, the decrease in skin surface temperature may cause the formation of substances that hinder penetration (such as an ice film), thus preventing the composition from reaching the skin surface. In this case, the penetration effect of the composition may decrease. Therefore, it is necessary to design the hybrid spraying system 100 while considering increasing the freezing ratio of the composition and maintaining the skin surface temperature at or above a suitable temperature; the specific design method will be described later.

[0147] As in the example described above, when the hybrid spraying system 100 undergoing cryogenic spraying is viewed from the side, the freezing ratio is calculated, and when the penetration effect is higher than that when the freezing ratio is 0%, the composition is frozen and sprayed at a freezing ratio equal to or higher than the calculated freezing ratio. This can be understood as cryogenic spraying.

[0148] The following will refer to Figures 3 to 6 The method for calculating the freezing ratio is described.

[0149] Figure 3 This is a view illustrating how the observation area OR is used to determine the freezing ratio of a composition according to one embodiment. Figure 3 (a) shows a designated observation area OR based on the hybrid spraying system 100; Figure 3 (b) and Figure 3 (c) shows the different freezing ratios in the observation area OR.

[0150] 2.3.1 Calculation of the freezing ratio of the composition in the observation area

[0151] High-speed cameras can be used to observe cryogenic spraying. Specifically, when a mixed spraying system 100 sprays a refrigerant and a composition, the refrigerant spray stream RSS, in which the composition is introduced, can be captured using a high-speed camera. The images or videos captured by the high-speed camera clearly show the morphology of the sprayed composition at a specific point in time or over a period of time, and the degree of cryogenicity of the composition can be determined from the images or videos.

[0152] You can specify an observation area (OR) to observe the freeze spraying. The observation area (OR) can refer to the area used to determine the freeze ratio.

[0153] The designated observation area (OR) is used to determine the freezing ratio of the composition reaching the skin surface. Since the composition is sprayed along with the refrigerant, freezing may occur in any area within the refrigerant spray stream RSS. However, because the purpose of cryo-spraying is to allow the composition to penetrate the skin, it is desirable to determine whether the composition actually reaching the skin surface was frozen or at what ratio. In other words, given that the purpose of cryo-spraying is to determine the freezing ratio affecting the composition's penetration, it is desirable to observe the area adjacent to the skin surface during cryo-spraying, rather than observing the entire area where the composition might be frozen.

[0154] The observation area (OR) can be specified based on the location on the skin surface where the composition needs to be sprayed. For example, refer to... Figure 3 (a) When the composition is sprayed onto the skin surface by the above-described hybrid spraying system 100, when the hybrid spraying system 100 is viewed from the side, the area spaced apart from the orifice of the nozzle 1500 of the hybrid spraying system 100 can be designated as the observation area OR, which corresponds to the separation distance between the orifice of the nozzle 1500 and the skin surface.

[0155] More specifically, when viewing the hybrid spraying system 100 from the left or right, a virtual first straight line L1 can be identified. This first straight line L1 is spaced apart from the orifice of the nozzle 1500 of the hybrid spraying system 100 by an observation distance OD and is orthogonal to the central axis CA of the nozzle 1500. Additionally, when viewing the hybrid spraying system 100 from the left or right, a second straight line L2 can be identified. This second straight line L2 is parallel to the first straight line L1 and is spaced apart from the first straight line L1 by an observation width OW in the direction toward (or away from) the nozzle 1500. The observation area OR can be defined as the region between the first straight line L1 and the second straight line L2.

[0156] The observation distance OD can be determined based on the recommended spraying distance. Alternatively, the observation distance OD can be determined based on the end of the distance holding unit, as described below. Alternatively, the observation distance OD can be determined based on the length of the distance holding unit.

[0157] Here, the recommended spraying distance can refer to the distance between the location where the mixing spraying system 100 needs to be positioned and the skin surface where the mixing spraying system 100 is used. Specifically, the recommended spraying distance can refer to the preferred straight-line distance between the nozzle 1500 and the skin surface when operating the mixing spraying system 100 to spray the refrigerant and composition onto the skin surface. The recommended spraying distance may be determined differently depending on the component specifications of the mixing spraying system 100 (e.g., the internal pressure of the refrigerant container RC, the size of the nozzle 1500 orifice, etc.).

[0158] It is recommended that the spraying distance be greater than the length of the acceleration section required for the composition to accelerate. Specifically, the composition is frozen after the refrigerant spray stream RSS is introduced, and the frozen composition is accelerated within a predetermined section. To sufficiently accelerate the frozen particles of the composition, an acceleration section of predetermined length needs to be provided in a direction parallel to the central axis CA of the nozzle 1500. For example, to sufficiently accelerate the frozen particles of the composition, an acceleration section of approximately 3 mm to approximately 5 mm or approximately 1 mm to approximately 10 mm is required. Preferably, the acceleration section described above is ensured based on the position where the composition introduces the refrigerant spray stream RSS. Therefore, based on a direction parallel to the central axis CA of the nozzle 1500, it is recommended that the spraying distance be set to be greater than the sum of the distance from the orifice of the nozzle 1500 to the position where the composition introduces the refrigerant spray stream RSS and the length of the acceleration section described above.

[0159] It is recommended that the spraying distance be greater than the length of the acceleration zone required for the composition to accelerate.

[0160] In addition, it is recommended that the spraying distance be greater than the length of the freezing section required for the composition to introduce the refrigerant spray stream RSS and be frozen.

[0161] Recommended spraying distances can be selected within, for example, a range of 3 mm to 100 mm. Furthermore, because recommended spraying distances are guidelines for preferred spraying distances, they can be presented as a range rather than specific values. For example, recommended spraying distances can be presented as a range of 3 mm to 100 mm with both a lower and upper distance limit.

[0162] The observation distance OD can be the same as the recommended spraying distance. When the observation distance OD is the same as the recommended spraying distance, the area of ​​the skin surface that is expected to be located can be designated as the observation area OR.

[0163] Meanwhile, the observation distance OD can be less than the recommended spraying distance. When using a high-speed camera to capture the process of spraying the composition and refrigerant onto the skin surface, it is difficult to determine the freezing ratio of the composition on the skin surface. Therefore, the freezing ratio determined at a predetermined distance from the skin surface can be estimated as the freezing ratio on the skin surface. In this case, the observation distance OD can be less than the recommended spraying distance. Alternatively, when viewing the mixing spraying system 100 from the side, the observation area OR can be determined by a first straight line L1 spaced apart from the skin surface by a first distance and a second straight line L2 parallel to the first straight line L1 and spaced apart from the first straight line L1 by an observation width OW.

[0164] The observation distance (OD) can be set to be greater than the recommended spraying distance. In this case, the freezing ratio within the observation area (OR) can also be estimated as the freezing ratio on the skin surface.

[0165] When the recommended spraying distance is presented as a range, the observation distance OD can be included within that range. The recommended spraying distance range can be defined as a segment from 3 mm to 100 mm.

[0166] At the same time, the observation distance (OD) does not necessarily have to be determined based on the recommended spraying distance; it can be determined arbitrarily.

[0167] The observation distance OD can be set to be greater than a minimum threshold distance. For the composition to be introduced into the refrigerant spray stream RSS and frozen, heat exchange between the refrigerant and the composition is required, and therefore, this heat exchange requires a predetermined amount of time. Because the composition moves with the refrigerant during heat exchange, the composition may not be frozen in the area closest to the nozzle 1500, through which the refrigerant is sprayed. Therefore, considering that the observation area OR is set to observe frozen particles, the observation distance OD can be set to be greater than the distance corresponding to the area closest to the nozzle 1500. For example, the observation distance OD can be set to be greater than a minimum threshold distance determined in the range of 0 mm to 3 mm.

[0168] The observation width OW refers to the width of the observation area OR.

[0169] The observation width OW can be determined to be within the range of 1% to 50% of the observation distance OD. Alternatively, the observation width OW can be determined to be the diameter of the refrigerant spray RSS at a position spaced apart from the orifice of nozzle 1500 by the observation distance OD. Alternatively, the observation width OW can be determined to be the average diameter of the refrigerant spray RSS. Meanwhile, the observation width OW can not be specified as an arbitrary value, and the interior of the refrigerant spray RSS visible to the naked eye can be used as the observation area OR.

[0170] The freezing ratio can be defined as the ratio of the number of solid composition particles to the total number of solid composition particles and liquid composition particles in a specific region. For example, refer to Figure 3 (b) or Figure 3 (c) The freezing ratio can be obtained by dividing the number of solid composition particles and the number of liquid composition particles observed in the statistical observation area OR by the sum of the number of solid composition particles and the number of liquid composition particles.

[0171] Meanwhile, the freezing ratio can further take into account the number of gas composition particles. However, since it is difficult to calculate the number of gas composition particles, and the composition is mostly in a solid or liquid state when the refrigerant is sprayed together with the composition, it is preferable that the freezing ratio does not take into account the number of gas composition particles.

[0172] The following will combine Figures 4 to 6 A method for identifying solid composition particles in captured images is described.

[0173] Figure 4 and Figure 5 An image showing a scene of spraying a liquid composition and a solid composition according to one embodiment. Figure 4 The image shown is captured by a high-speed camera when light is emitted toward a spraying system 100 that mixes the spraying composition with a refrigerant. Figure 5 The image shows a spraying system 100 in which the spraying composition and refrigerant are mixed and captured by a high-speed camera, with light emitted toward the high-speed camera and blocked by the composition.

[0174] Figure 6 A view illustrating an image processing procedure for statistical analysis of solid composition particles according to one embodiment. Figure 6 (a) shows an image of the observation region OR. Figure 6 (b) shows the results of the study on the topic. Figure 6 (a) The image obtained by applying a threshold filter, and Figure 6 (c) shows the... Figure 6 (b) The solid composition particles in the image are tracked.

[0175] In calculating the freezing ratio, solid composition particles and liquid composition particles can be visually distinguished from images or videos (hereinafter referred to as "images, etc.") taken from a high-speed camera. Specifically, refer to Figure 4 Because the solid composition particles are in crystalline form, they reflect light and appear relatively bright.

[0176] Therefore, among the particles visually identified in images captured by high-speed cameras, particles that reflect light and appear bright can be designated as solid composition particles, while particles that do not reflect light and appear dim can be designated as liquid composition particles.

[0177] In addition, such as Figure 5 As shown, liquid composition particles and solid composition particles can be distinguished based on the brightness of the composition particles in images captured by high-speed cameras, etc. (Reference) Figure 5 Because solid composition particles are darker than liquid composition particles, solid composition particles can be distinguished from liquid composition particles based on a predetermined level of brightness.

[0178] refer to Figure 6 The observation area OR is separated from images captured by a high-speed camera, and a filter is applied to the observation area OR to select pixels with brightness equal to or lower than a predetermined level of brightness. Pixels occupying more than the predetermined area are tracked to count the particles of the solid composition.

[0179] In addition to the methods described above for identifying particles in solid compositions, dynamic light scattering (DLS) with polarization analysis, time-resolved X-ray diffraction (TR-XRD), or in-situ spectroscopy can also be used.

[0180] Meanwhile, the freezing ratio can be defined as the ratio of the area of ​​solid composition particles to the sum of the areas of solid composition particles and liquid composition particles within a specified area.

[0181] According to one implementation plan, the freezing ratio can be calculated as follows.

[0182] First, images can be acquired using a high-speed camera when the composition and refrigerant are sprayed together through a mixing spraying system 100. Then, an observation area OR can be specified in the acquired images, and the freezing ratio can be calculated within the specified observation area OR.

[0183] Multiple images can be obtained here.

[0184] For example, the mixing spraying system 100 can perform n (n is a natural number equal to or greater than 2) freeze spraying operations, and during the nth test freeze spraying operation, the nth test image captured at a preset time point after the start of spraying can be obtained. Subsequently, the nth test freeze ratio can be calculated from the nth test image, and the average value of the first freeze ratio to the nth test freeze ratio can be obtained as the final freeze ratio. Here, performing n freeze spraying operations can be understood as performing n spraying operations of the composition and refrigerant under the condition that the same amount of refrigerant is stored in the refrigerant container RC at the same pressure and the same amount of composition is stored in the composition container CC.

[0185] For example, a refrigerant and composition can be sprayed from a mixed spraying system 100 during a preset capture time, and at least two or more images can be acquired from the images obtained during the capture time. An observation area OR can be specified and a freezing ratio can be calculated from each captured image, and the average freezing ratio of each captured image can be obtained as the final freezing ratio.

[0186] Meanwhile, when acquiring multiple images, in addition to averaging the freezing ratios obtained from each image, the freezing ratio can be calculated by adding the number of solid composition particles and the number of liquid composition particles counted in each image.

[0187] As described below, the permeation effect of the composition may vary depending on the freezing ratio. For example, the permeation effect of the composition may increase as the freezing ratio increases.

[0188] Therefore, the hybrid spraying system 100 needs to be designed to find a freezing ratio that achieves a significant composition penetration effect and to perform freeze spraying at the corresponding freezing ratio.

[0189] The calculation of the freezing ratio in the observation area OR has been described above and understood as freezing spraying, but the technical concept of this disclosure is not limited thereto.

[0190] For example, when the number of frozen particles in the observation area OR is equal to or greater than a preset threshold number of particles when the composition is sprayed together with the refrigerant, it can be understood as frozen spraying.

[0191] Here, the threshold particle number is the particle number value at which the composition has a higher penetration effect on the skin than when the number of frozen particles is essentially zero, and it can be specified experimentally.

[0192] Meanwhile, the method for counting the number of frozen particles in the observation area OR is the same as the method for counting the number of frozen particles in the composition in the freezing ratio calculation method described above.

[0193] The foregoing has described methods for specifying the observation area OR and calculating the freezing ratio when viewing the mixed spraying system 100 from the side or when viewing the spraying composition and refrigerant from the side. However, the technical concept of this disclosure is not limited thereto, and it is also possible to specify the observation area OR and calculate the freezing ratio when viewing the mixed spraying system 100 from above or below or when viewing the spraying composition and refrigerant from above or below. Furthermore, it is also possible to calculate the freezing ratio by statistically analyzing the solid composition particles versus the liquid composition particles when viewing from two or more directions.

[0194] Similarly, when viewed from a direction other than the side or from two or more directions, the freezing ratio with significant penetration effect can be calculated experimentally, and spraying the composition and refrigerant at a freezing ratio equal to or greater than the corresponding freezing ratio can be understood as freezing spraying.

[0195] 2.3.2 Calculate the freezing ratio of the composition crossing the observation line.

[0196] The freezing ratio can be calculated based on the observation line OL below.

[0197] Figure 7 This is a view illustrating how the freezing ratio is calculated using the observation line OL according to one implementation scheme. Figure 7 (a) shows a designated observation line OL based on the hybrid spraying system 100, and Figure 7 (b) Shows the composition particles that cross the observation line OL at the first and second time points.

[0198] The observation line (OL) can be specified based on the location on the skin surface where the composition needs to be sprayed. For example, refer to... Figure 6 (a) When viewing the mixed spraying system 100 of the spraying composition from the side, a straight line spaced at a predetermined distance from the mixed spraying system 100 can be designated as the observation line OL. More specifically, when viewing the mixed spraying system 100 from the left or right, a virtual straight line spaced at an observation distance OD from the orifice of the nozzle 1500 of the mixed spraying system 100 and orthogonal to the central axis CA of the nozzle 1500 can be designated as the observation line OL.

[0199] Here, the observation distance OD is the same as that described in the observation area OR.

[0200] The freezing ratio can be calculated as the ratio of the number of frozen particles of the composition crossing the observation line OL within a predetermined time period to the sum of the number of solid composition particles and the number of liquid composition particles. More specifically, refer to... Figure 7(b) The freezing ratio can be calculated as follows. First, an image can be acquired by capturing the side of the mixing spraying system 100 of the spraying composition using a high-speed camera. Then, in the image, an image frame corresponding to a random first time point and an image frame corresponding to a second time point are selected. Finally, in the selected image frames, the number of liquid composition particles and the number of solid composition particles crossing the observation line OL during the period from the first time point to the second time point can be counted.

[0201] The freezing ratio can be obtained as the average of the independent freezing ratios calculated from multiple images. Here, multiple images may include images obtained from each of the nth experimental freezing spraying processes. Furthermore, multiple images may refer to images acquired over n time periods from images captured by the mixed spraying system 100 spraying composition and refrigerant over a predetermined time period.

[0202] As described in the observation area OR, the method of calculating the freezing ratio using the observation line OL can also assume that the mixed spraying system 100 is viewed from above, below, or from two or more directions, as well as from the side.

[0203] 2.3.3 Calculate the freezing ratio of the composition sprayed onto the observation surface.

[0204] The freezing ratio can be calculated using the following observation surfaces.

[0205] First, the observation surface can be placed at a distance OD from the observation point in the mixed spraying system 100, and the composition and refrigerant can be sprayed onto the observation surface, while a high-speed camera captures the observation surface.

[0206] Subsequently, image frames corresponding to the time point when the composition first arrives at the observation surface or a predetermined time point after that time point can be obtained from images captured by the high-speed camera.

[0207] Solid compositions and liquid compositions can be distinguished based on color differences (or brightness differences) on the observation surface of the acquired image frames, and therefore, the area occupied by the solid composition and the area occupied by the liquid composition can be calculated based on the observation surface.

[0208] The freezing ratio can be calculated as the ratio of the area occupied by the solid composition to the sum of the areas occupied by the solid composition and the liquid composition.

[0209] In methods for calculating the freezing ratio using an observation surface, sensors capable of distinguishing between liquids and solids can be used in addition to high-speed cameras. For example, while spraying the composition and refrigerant onto an insulation panel, the temperature change of the insulation panel can be monitored. The freezing ratio can be calculated based on the temperature change of the insulation panel, the amount of cooling energy (or heat) required to maintain the temperature of the insulation panel, and the amount of latent heat absorbed when the frozen particles turn into liquid. As another example, an electrical contact sensor can be mounted on the observation surface, and considering the capacitance of the liquid and solid compositions when in contact with the observation surface, the freezing ratio can be estimated based on the measured changes in the electrical signal.

[0210] In the method of calculating the freezing ratio using the observed surface, an electrical contact sensor is used.

[0211] 2.4 Methods for generating frozen particles

[0212] The following will refer to Figures 8 to 11 A method for generating frozen particles using a freezing composition is described.

[0213] As described above, the mixed spraying system 100 can be used to generate frozen particles of the composition. Specifically, a relatively low-temperature refrigerant spray stream RSS can be formed by the refrigerant spraying device 1000 of the mixed spraying system 100, and frozen particles can be generated when the composition is supplied to the refrigerant spray stream RSS by the composition supply device 2000 of the mixed spraying system 100.

[0214] Figure 8 A view illustrating a hybrid spraying system 100 according to one embodiment. Reference Figure 8 The mixed spraying system 100 may include a refrigerant spraying device 1000 and a composition supply device 2000. The composition supply device 2000 may be connected to the nozzle 1500 of the refrigerant spraying device 1000.

[0215] At the same time, such as Figure 8 As shown, the mixing spraying system 100 may further include a cover COV that covers the nozzle 1500 and supports the composition supply device 2000.

[0216] For ease of explanation, the following description will depict the composition supply device 2000 connected to the nozzle 1500 of the refrigerant spraying device 1000, but the technical concept of this disclosure is not limited thereto. In addition to the nozzle 1500, the composition supply device 2000 may also be connected to a cover COV or the housing of the refrigerant spraying device 1000. However, even in this case, the composition guide 2100 of the composition supply device 2000 needs to be configured adjacent to the nozzle 1500 of the refrigerant spraying system 1000, such that the composition discharged from the composition guide 2100 is introduced into the refrigerant spray stream RSS formed from the nozzle 1500.

[0217] 2.4.1 Detailed Components of the Hybrid Spraying System

[0218] Figure 9 A view showing components of a refrigerant spraying apparatus 1000 according to one embodiment. Reference Figure 9 The refrigerant spraying device 1000 may include a container receiving unit 1100, a flow regulating unit 1200, a heating unit 1300, a nozzle connection unit 1400, a nozzle 1500, a sensor unit 1600, an input unit 1700, an output unit 1800, and a controller 1900.

[0219] The container receiving unit 1100 can accommodate a refrigerant container RC. The container receiving unit 1100 is provided with a refrigerant receiving section for the introduction of refrigerant. The refrigerant receiving section can be understood as a component including a flow path or orifice for the movement of refrigerant.

[0220] For example, the refrigerant container RC can be configured as a portable sleeve, and the refrigerant container RC can be installed on or removed from the container receiving unit 1100. When the refrigerant container RC is installed on the container receiving unit 1100, the refrigerant in the refrigerant container RC can move to the refrigerant receiving section of the container receiving unit 1100.

[0221] When the refrigerant container RC is configured as a sleeve and installed on the container receiving unit 1100, it may be necessary to have components for piercing the sleeve inlet to allow refrigerant to exit from the sleeve and components for sealing the pierced sleeve inlet to prevent refrigerant leakage to the outside. Therefore, the piercing components and the sealing components may be located between the container receiving unit 1100 and the refrigerant container RC.

[0222] For example, the refrigerant container RC can be configured as a difficult-to-carry storage tank, and the container receiving unit 1100 can be connected to the refrigerant container RC via a pipe. The refrigerant in the refrigerant container RC can be moved to the refrigerant receiving section of the container receiving unit 1100 via the pipe.

[0223] The flow regulating unit 1200 can control the movement of refrigerant. For example, the flow regulating unit 1200 may include a valve, and depending on whether the valve is open or closed, the refrigerant may or may not move. Furthermore, the degree of refrigerant movement depends on the valve opening ratio.

[0224] Here, the valve may be a solenoid valve, but the technical concept of this disclosure is not limited to this.

[0225] The container receiving unit 1100 and the flow regulating unit 1200 are fluidly connected to each other, allowing refrigerant introduced into the refrigerant receiving section of the container receiving unit 1100 to move to the flow regulating unit 1200. For example, the flow paths of the refrigerant receiving section of the container receiving unit 1100 and the flow regulating unit 1200 can be directly connected to each other. Alternatively, the refrigerant receiving section of the container receiving unit 1100 and the flow regulating unit 1200 can be connected to each other via pipes.

[0226] As described later, the refrigerant spraying device 1000 may be equipped with a precise temperature control function to accurately control the temperature of the spraying area where the refrigerant is sprayed. The heating unit 1300 is one of the means to achieve the precise temperature control function and can provide heat to the refrigerant before spraying.

[0227] To achieve precise control of the temperature in the spraying area, the refrigerant spraying device 1000 can use the heating unit 1300 to heat the high-pressure / low-temperature refrigerant before spraying the refrigerant.

[0228] The heating unit 1300 may include a heat source and a heat transfer medium. The heat source is a component that generates heat and may include, for example, elements that utilize thermoelectric effects such as the Peltier effect. In this case, the amount of heat energy generated by the heat source may vary depending on the amount of power or current supplied to the heat source. The heat transfer medium provides the heat generated by the heat source to the refrigerant. For example, the heat transfer medium may receive heat energy from the heat source and transfer the received heat energy to the refrigerant.

[0229] The heat transfer medium can be configured in various forms. For example, a heat source can be thermally connected to the heat transfer medium, at least one flow path for the refrigerant to move can be formed inside the heat transfer medium, and therefore, components can be provided to maximize the contact area (i.e., heat transfer area) between the heat transfer medium and the refrigerant.

[0230] The flow regulating unit 1200 and the heating unit 1300 can be fluidly connected to each other, allowing refrigerant to move from the flow regulating unit 1200 to the heating unit 1300. For example, the flow paths of the flow regulating unit 1200 and the heating unit 1300 can be directly connected to each other. Alternatively, the flow regulating unit 1200 and the heating unit 1300 can be connected to each other via pipes.

[0231] Refrigerant can be sprayed through nozzle 1500. A flow path for the refrigerant is formed inside nozzle 1500. The width of the flow path formed in nozzle 1500 at the refrigerant discharge end is narrower than the width at the refrigerant inlet end. Before the refrigerant is sprayed from the other end of nozzle 1500, the refrigerant is maintained at high pressure, and the refrigerant sprayed from the other end of nozzle 1500 is sprayed at high speed and rapidly cooled while undergoing adiabatic expansion. Here, the higher the refrigerant pressure introduced into nozzle 1500, the lower the temperature of the adiabatic expanding refrigerant and the higher the speed. For example, when the internal pressure of the refrigerant container RC is 50 bar, the pressure of the refrigerant introduced into nozzle 1500 can also be close to 50 bar, and the temperature of the refrigerant sprayed from nozzle 1500 can be approximately -50°C. If the low-temperature refrigerant with the high pressure required for high-speed spraying is directly sprayed onto the skin, it may cause cell necrosis. To prevent skin damage such as cell necrosis, heat energy can be applied using the heating unit 1300 described above before spraying the refrigerant.

[0232] Nozzle 1500 can be attached to and detached from refrigerant spraying device 1000. Nozzle connection unit 1400 can be provided to attach nozzle 1500 to and detach from refrigerant spraying device 1000.

[0233] The composition supply device 2000 can be mounted on the nozzle 1500. For example, a portion of the composition supply device 2000 can be connected to the nozzle 1500 such that the output end of the composition guide 2100 of the composition supply device 2000 is positioned adjacent to the orifice of the nozzle 1500.

[0234] Meanwhile, the flow regulating unit 1200, the heating unit 1300, and the nozzle 1500 are fluidly connected to each other and arranged in various ways. For example, the heating unit 1300 may be disposed between the flow regulating unit 1200 and the nozzle 1500, such that the refrigerant flows through the flow regulating unit 1200 and reaches the heating unit 1300, and also flows through the heating unit 1300 and reaches the nozzle 1500. As another example, the flow regulating unit 1200 may be disposed between the heating unit 1300 and the nozzle 1500, such that the refrigerant flows through the heating unit 1300 and reaches the flow regulating unit 1200, and also flows through the flow regulating unit 1200 and reaches the nozzle 1500.

[0235] Sensor unit 1600 can measure the temperature of the area where the refrigerant is sprayed. For example, sensor unit 1600 can measure the temperature of the skin surface where the refrigerant is sprayed and provide the measurement information to controller 1900.

[0236] Simultaneously, sensor unit 1600 can measure the temperature of certain components of composition supply device 2000. For example, sensor unit 1600 can measure the temperature of composition guide 2100 or mixing unit 2300 and provide the measurement information to controller 1900.

[0237] Input unit 1700 can receive user input. For example, input unit 1700 may include at least one push-button switch and can provide a push-button input signal to controller 1900 in response to user pressure on the switch, and controller 1900 can control the opening and closing of flow regulating unit 1200 based on the push-button input signal. Additionally, input unit 1700 may include at least one rotary switch and can provide a rotary input signal to controller 1900 in response to user operation, and controller 1900 can set a target temperature or target time based on the rotary input signal. Here, target temperature refers to the temperature to be achieved by adjusting the temperature of the sprayed area. Target time refers to the time required to maintain the sprayed refrigerant or the time required to maintain the temperature of the sprayed area at the target temperature. Furthermore, the user can use input unit 1700 to set the target penetration depth of the composition. As described later, the mixing spraying system 100 can control the size of the frozen particles and thus adjust the penetration depth by controlling the heat applied to the refrigerant or the flow rate of the composition.

[0238] The output unit 1800 can output an interface and various information for use by the refrigerant spraying device 1000 to the user. For example, the output unit 1800 may include a display, and the output unit 1800 can output an interface for setting the target temperature or target time mentioned above through the display. While the refrigerant spraying device 1000 is operating, the output unit 1800 can output information such as the real-time temperature of the spraying area or the total time for spraying refrigerant as measured by the sensor unit 1600.

[0239] The controller 1900 can control various components of the refrigerant spraying device 1000. For example, the controller 1900 can control the temperature of the sprayed refrigerant by controlling the heating unit 1300, control the flow rate of the refrigerant by controlling the flow regulating unit 1200, and output specific information to the user by the output unit 1800.

[0240] The refrigerant spraying device 1000 can be operated in the following manner.

[0241] First, the controller 1900 can set the target temperature and target time. For example, the controller 1900 can provide an interface through the output unit 1800 to guide the user in setting the target temperature and target time, and receive setting input signals in response to user operations through the input unit 1700, and set the target temperature and target time based on the received setting input signals.

[0242] Subsequently, the controller 1900 can output information indicating to the user that the operation preparation is complete through the output unit 1800, receive the start input signal in response to the user operation through the input unit 1700, and enable the refrigerant to be sprayed based on the received start input signal.

[0243] When spraying refrigerant, the controller 1900 can precisely cool the sprayed area. For example, when spraying refrigerant, the controller 1900 can acquire the real-time temperature of the sprayed area measured by the sensor unit 1600, and control the heating unit 1300 by comparing the acquired real-time temperature with a set target temperature. Specifically, when the acquired temperature value is lower than the target temperature, the controller 1900 can increase the heat energy applied to the refrigerant through the heating unit 1300, and when the acquired temperature value is higher than the target temperature, the controller 1900 can decrease the heat energy applied to the refrigerant through the heating unit 1300. Here, the controller 1900 can use proportional-integral-derivative (PID) control as a feedback control technique.

[0244] When precise cooling is achieved via controller 1900, the temperature of the sprayed area can be controlled within a predetermined error range based on the target temperature.

[0245] Meanwhile, the controller 1900 uses the heating unit 1300 to provide heat to the refrigerant, regardless of the temperature of the spraying area. For example, the controller 1900 can control the heating unit 1300 to provide heat energy every predetermined unit of time. In this case, temperature measurement of the spraying area is not required.

[0246] although Figure 9 As not shown, the refrigerant spraying apparatus 1000 may further include a distance maintaining unit. When spraying refrigerant onto the spraying area, it is preferable to keep the distance between the target area and the refrigerant spraying apparatus 1000 constant. For example, it is preferable to spray the refrigerant and the composition simultaneously when the nozzle 1500 of the refrigerant spraying apparatus 1000 is within a recommended spraying distance range relative to the target area.

[0247] In particular, when it is necessary to measure and monitor the temperature of the spraying area in the refrigerant spraying device 1000 (for example, when using the temperature of the target area for feedback control, when the temperature of the target area drops to or below the safe temperature and the device stops operating, or when the real-time temperature of the target area is output to the user), the temperature of the spraying area needs to be accurately measured.

[0248] The distance holding unit can be located adjacent to the nozzle 1500. The distance holding unit can be connected to the housing of the refrigerant spraying apparatus 1000. The length of the distance holding unit can be designed such that the distance from the orifice of the nozzle 1500 to the end of the distance holding unit in a direction parallel to the central axis CA of the nozzle 1500 is within a recommended spraying distance range. For example, the length of the distance holding unit can be determined based on the composition freezing ratio maintaining a spraying distance equal to or greater than a predetermined value.

[0249] Furthermore, the refrigerant spraying device 1000 is not limited to the embodiments described above, and any device or structure that performs the function of spraying refrigerant by being directly connected to the refrigerant container RC or indirectly connected to the refrigerant container RC by means of a pipe can be regarded as the refrigerant spraying device 1000 described in this disclosure. For example, the refrigerant spraying device 1000 may not heat the refrigerant, and therefore, the heating unit 1300 and the sensor unit 1600 may be omitted.

[0250] Figure 10 A view showing the composition supply device 2000 according to the first embodiment. Figure 10 (a) A composition supply device 2000 connected to nozzle 1500 is shown. Figure 10 (b) shows the composition being mixed with refrigerant and sprayed at section A-A' when the composition supply device 2000 is connected to the nozzle 1500.

[0251] refer to Figure 10 The composition supply device 2000 may include a composition guide 2100, a mixing unit 2300, a composition container CC, and a connecting part 2400.

[0252] The composition guide 2100 is used to guide the movement of the composition. For example, such as... Figure 10 As shown in (b), the composition guide 2100 is fluidly connected to the composition container CC and the mixing unit 2300, and the composition stored in the composition container CC can be moved to the mixing unit 2300 via the composition guide 2100. The composition guide 2100 can be implemented in the form of a tube. The composition guide 2100 may include an input end and an output end, through which the composition is introduced and discharged.

[0253] The mixing unit 2300 provides a mixing space MS for the mixed composition and refrigerant. For example... Figure 10As shown in (b), the mixing unit 2300 has an inner surface defining a mixing space MS. The output end of the composition guide 2100 may be located on the inner surface of the mixing unit 2300. The mixing space MS may be fluidly connected to the nozzle 1500 of the refrigerant spraying apparatus 1000, and a refrigerant spray stream RSS may be formed in the mixing space MS when refrigerant is sprayed from the nozzle 1500.

[0254] The refrigerant spray stream RSS can be divided into the main stream S1 and the secondary stream S2. The main stream S1 refers to the area with relatively strong refrigerant spray intensity, while the secondary stream S2 refers to the area with relatively weak refrigerant spray intensity. Alternatively, the main stream S1 can refer to the area with relatively high refrigerant density, while the secondary stream S2 can refer to the area with relatively low refrigerant density.

[0255] The main stream S1 and the tributary S2 can be defined based on the central axis CA of the nozzle 1500. For example, when the refrigerant spray RSS is intercepted perpendicular to the central axis CA of the nozzle 1500, the main stream S1 can be located within the boundary distance of the central axis CA of the nozzle 1500, while the tributary S2 can be located beyond the boundary distance of the central axis CA of the nozzle 1500. The boundary distance may vary depending on the distance from the end of the nozzle 1500, the internal pressure of the refrigerant container RC, and the size of the orifice of the nozzle 1500. For another example, the region in the refrigerant spray RSS where the refrigerant temperature is equal to or less than the threshold temperature can be the main stream S1, while the remaining region can be the tributary S2. For yet another example, the region in the refrigerant spray RSS where the average velocity is equal to or greater than the threshold velocity can be the main stream S1, while the remaining region can be the tributary S2. For yet another example, the region in the refrigerant spray RSS where the refrigerant density is equal to or greater than the threshold density can be the main stream S1, while the remaining region can be the tributary S2.

[0256] Simultaneously, it is important that the composition is introduced into the mainstream S1 of the refrigerant spray stream RSS. This is because the refrigerant velocity in the mainstream S1 is faster than that in the secondary stream S2, and the temperature of the refrigerant in the mainstream S1 is lower than that in the secondary stream S2. Therefore, when the composition contacts and sprays the refrigerant particles in the mainstream S1, rather than in the secondary stream S2, the temperature of the composition decreases and the spraying speed increases.

[0257] The composition container CC may store the composition therein. The composition container CC may have an injection port through which the composition is injected. The composition container CC may have a vent hole through which external air is introduced.

[0258] The coupling 2400 refers to the component in the composition supply device 2000 that is connected to the nozzle 1500. For example, the coupling 2400 may include a hook coupling member, a threaded coupling member, or a force-fitting coupling member, and may be connected to and fixed to a region of the nozzle 1500.

[0259] When a refrigerant spray stream (RSS) is formed in the mixing space (MS), refrigerant is sprayed near the output end of the composition guide 2100, and according to Bernoulli's principle, a negative pressure is formed at the output end of the composition guide 2100. Because the composition container (CC) has a vent, its internal pressure can be maintained at atmospheric pressure. Therefore, the composition stored in the composition container (CC) moves towards the output end of the composition guide 2100, which forms a lower pressure, and is thus introduced into the refrigerant spray stream (RSS).

[0260] Simultaneously, a guide plate for moving the composition to the mainstream S1 of the refrigerant spray RSS can be assembled in the mixing unit 2300. The guide plate includes a surface with a predetermined length. A first end of the guide plate can be positioned adjacent to the output end of the composition guide 2100, while a second end of the guide plate can be positioned adjacent to the mainstream S1. Therefore, the composition introduced by the composition guide 2100 can move along the guide plate and reach the mainstream S1.

[0261] The components of the composition supply device 2000 may be manufactured as a single unit. Alternatively, at least some of the components of the composition supply device 2000 may be manufactured separately and interconnected.

[0262] Figure 11 A view showing the composition supply device 2000 according to the second embodiment. Figure 11 (a) shows a composition supply device 2000 connected to nozzle 1500, and Figure 11 (b) shows the composition being mixed with refrigerant and sprayed at section B-B' when the composition supply device 2000 is connected to the nozzle 1500.

[0263] refer to Figure 11 The composition supply device 2000 may include a composition guide 2100, a composition container CC, an actuator 2200, and a coupling 2400.

[0264] The composition guide 2100 is a component that receives the composition from the composition container CC and supplies the composition to the refrigerant spray stream RSS. The composition guide 2100 may include an inlet and an outlet, with the composition introduced through the inlet and discharged through the outlet.

[0265] refer to Figure 11 (b) A composition flow path for the composition to move is formed inside the composition guide 2100, and the output end of the composition guide 2100 can be positioned adjacent to the orifice of the nozzle 1500. Specifically, the output end of the composition guide 2100 can be positioned at a first distance from the orifice of the nozzle 1500 in a direction parallel to the central axis CA of the nozzle 1500, and at a second distance from the orifice of the nozzle 1500 in a direction orthogonal to the central axis CA of the nozzle 1500. Here, the output end of the composition guide 2100 can be positioned to contact the main stream S1 of the refrigerant spray RSS formed by the nozzle 1500. For example, the first distance and the second distance can be determined based on the boundary between the main stream S1 and the branch stream S2 of the refrigerant spray RSS. The positional relationship between the output end of the composition guide 2100 and the nozzle 1500 will be described later.

[0266] The composition container CC is a component that internally stores the composition. The composition container CC may have an injection port through which the composition is injected. The composition container CC may be fluidly connected to the actuator 2200. The composition inside the composition container CC may be pressurized by the actuator 2200 and moved towards the composition guide 2100.

[0267] The actuator 2200 may be configured to supply fluid to the mixing unit 2300 at a preset flow rate. For example, the actuator 2200 may include a piston and an electric motor, and may pressurize the fluid by receiving power and moving the piston.

[0268] Since the connecting part 2400 is the same as the connecting part described above, its description will be omitted.

[0269] refer to Figure 11 (b) When the refrigerant spraying device 1000 forms a refrigerant spray stream RSS, the actuator 2200 of the composition supply device 2000 is operable to pressurize the composition in the composition container CC, causing the composition to be introduced into the refrigerant spray stream RSS through the composition guide 2100. Here, the flow regulating unit 1200 and the actuator 2200 can be controlled by the controller 1900. For example, the flow regulating unit 1200 is operated first to spray the refrigerant, and then the actuator 2200 is operated to discharge the composition. As another example, the flow regulating unit 1200 and the actuator 2200 can be operated simultaneously.

[0270] The refrigerant spraying apparatus 1000 and the composition supply apparatus 2000 have been described above as being manufactured separately and connected to each other, but the technical concept of this disclosure is not limited thereto. For example, some components of the composition supply apparatus 2000 may be mounted on the refrigerant spraying apparatus 1000, while some components of the refrigerant spraying apparatus 1000 may be implemented in the composition supply apparatus 2000. Specifically, the composition supply apparatus 2000 may include components that perform the function of the nozzle 1500, and the composition supply apparatus 2000 may be connected to the nozzle coupling unit 1400 of the refrigerant spraying apparatus 1000.

[0271] As described above, the refrigerant spray stream RSS can be formed by the refrigerant spraying device 1000, and the composition can be introduced into the refrigerant spray stream RSS through the composition supply device 2000. The composition introduced into the refrigerant spray stream RSS can be broken into particles within the refrigerant spray stream RSS and frozen by heat exchange with the relatively low-temperature refrigerant. Here, the particle size can be from about 10 μm to about 300 μm. Alternatively, the particle size can be from about 10 μm to about 100 μm.

[0272] However, as will be described below, depending on the design and control methods of the mixing spraying system 100, the composition may or may not be frozen, and the freezing ratio may vary.

[0273] 2.4.2 Factors Affecting the Formation of Frozen Particles

[0274] First, factors involved in whether the composition is frozen and at what rate it is frozen may include the temperature of the refrigerant spray RSS, the composition flow rate, and the location where the composition enters.

[0275] As the temperature of the refrigerant spray stream RSS decreases, the composition can be easily frozen. Here, the temperature of the refrigerant spray stream RSS may refer to the temperature measured at a specific point within the refrigerant spray stream RSS (e.g., the temperature at a specific point spaced a predetermined distance from the orifice of nozzle 1500). Alternatively, the temperature of the refrigerant spray stream RSS may refer to the average temperature of at least one region of the refrigerant spray stream RSS. As the temperature of the refrigerant particles exchanging heat with the composition decreases, the temperature of the composition may decrease, thereby increasing the probability of freezing the composition. Furthermore, as the temperature of the refrigerant particles decreases, the freezing rate of the composition may increase.

[0276] Meanwhile, excessively lowering the temperature of the refrigerant spray RSS to freeze the composition may cause pain or irreversible damage to the skin. Therefore, the temperature of the refrigerant spray RSS needs to be controlled so that the composition does not cause pain or damage to the skin when frozen.

[0277] Additionally, when the temperature of the refrigerant spray RSS drops excessively, moisture on the skin surface may be frozen, forming a substance that hinders penetration (such as an ice film), and the composition may not be able to reach the skin surface and bounce off the ice film.

[0278] The temperature of the refrigerant spray stream RSS may vary depending on the refrigerant pressure before it is sprayed from nozzle 1500. For example, as the refrigerant pressure before spraying from nozzle 1500 increases, the temperature of the refrigerant spray stream RSS may decrease. This is because as the refrigerant pressure before spraying increases, the difference between it and the refrigerant pressure after spraying (atmospheric pressure) increases, and the temperature drop increases accordingly.

[0279] The refrigerant pressure before spraying can be basically the same as the internal pressure of the refrigerant container RC. In other words, as the internal pressure of the refrigerant container RC increases, the refrigerant pressure before spraying may increase and the temperature of the refrigerant spray stream RSS may decrease.

[0280] Therefore, a refrigerant container RC with high internal pressure can be used to freeze the composition or increase the freezing ratio of the composition. Alternatively, the refrigerant container RC can be heated to increase the pressure inside the refrigerant container RC.

[0281] Meanwhile, in order to increase the refrigerant pressure before spraying, the refrigerant spraying device 1000 may further include a compressor. For example, the compressor may be located between the nozzle 1500 and the flow regulating unit 1200, or between the flow regulating unit 1200 and the container receiving unit 1100, to increase the refrigerant pressure.

[0282] The temperature of the refrigerant spray stream RSS may vary depending on the degree of heating of the refrigerant before spraying from nozzle 1500. As the amount of heated refrigerant increases, the temperature of the refrigerant spray stream RSS may rise. This is because the increased refrigerant temperature before spraying and the increased gas ratio in the refrigerant reduce the amount of refrigerant that expands.

[0283] The amount of refrigerant being heated can be adjusted by the heating unit 1300 of the refrigerant spraying device 1000. For example, when the heating unit 1300 is a thermoelectric element that receives power and generates heat, the heat energy supplied from the heating unit 1300 to the refrigerant per unit time can be adjusted by adjusting the power applied to the heating unit 1300.

[0284] The amount of refrigerant being heated can be controlled so that the temperature of the skin surface is equal to or higher than the minimum temperature that would cause skin damage or pain. For this purpose, the controller 1900 of the refrigerant spraying device 1000 can use the difference between the real-time temperature of the target area and the minimum temperature for feedback control.

[0285] The temperature of the refrigerant spray stream RSS can be controlled by methods such as controlling the refrigerant pressure before spraying, controlling the heat energy applied to the refrigerant, or a combination thereof.

[0286] As the composition flow rate decreases, the composition can be easily frozen. Composition flow rate refers to the amount of composition introduced into the refrigerant spray stream RSS per unit time. Alternatively, composition flow rate refers to the amount of composition supplied per unit time by composition guide 2100.

[0287] Because the composition introduced into the refrigerant spray RSS receives cooling energy from the refrigerant spray RSS (reducing its temperature through heat exchange), as the composition flow rate increases, the cooling energy received per unit mass of composition decreases, so the composition may not be able to be frozen or the freezing ratio may decrease.

[0288] Simultaneously, as the composition flow rate decreases, the total amount of refrigerant used to spray a specific amount of composition onto the target area may increase. That is, when the composition flow rate is reduced excessively, the total amount of refrigerant used to spray a specific amount of composition may increase excessively, thereby increasing the cost and time required for cryo-spraying. Alternatively, when the composition flow rate is reduced excessively and a predetermined amount of refrigerant is used, the amount of composition sprayed may be reduced excessively, thereby reducing the amount of composition that penetrates into the skin.

[0289] Therefore, the flow rate of the composition needs to be controlled so that the composition is frozen during the predetermined treatment time and the amount of composition supplied is equal to or higher than the predetermined level.

[0290] The flow rate of the composition can be adjusted using actuator 2200. For example, when supplying the composition to composition guide 2100, actuator 2200 can be used to control the pressure applied to the composition to be constant, and the flow rate of the composition can be controlled to be constant depending on the pressure. As the pressure applied to the composition increases, the flow rate of the composition increases; as the pressure applied to the composition decreases, the flow rate of the composition decreases.

[0291] When the composition guide 2100 includes a conduit, the composition flow rate can be adjusted depending on the width of the conduit. Even when the composition is supplied from the composition container CC to the composition guide 2100 through the conduit, the composition flow rate can still be adjusted depending on the width of the conduit. In other words, the composition flow rate can be determined based on the width of the conduit designed during its manufacture. As the conduit width increases, the composition flow rate increases; as the conduit width decreases, the composition flow rate decreases.

[0292] The flow rate of the composition can be controlled by using the actuator 2200, designing the pipe width of the composition guide 2100 or the pipe width connected to the composition guide 2100, or a combination thereof.

[0293] The closer the composition flows into the nozzle 1500, the better it is likely to be frozen. When the composition and refrigerant are sprayed onto the skin surface using the mixing spray system 100, the composition is cooled by the refrigerant spray RSS from the point where it flows into the refrigerant spray stream RSS until it reaches the skin surface.

[0294] In other words, as the distance between the location where the composition is introduced and the skin surface increases, the time required for the composition to be cooled by the refrigerant spray RSS increases, thereby increasing the likelihood of the composition being frozen or the freezing ratio of the composition. Alternatively, as the distance between the location where the composition is introduced and the orifice of nozzle 1500 decreases, the time required for the composition to be cooled by the refrigerant spray RSS increases, thereby increasing the likelihood of the composition being frozen or the freezing ratio of the composition.

[0295] However, the composition inflow location can be understood as the location of the output end of the composition guide 2100, and when the output end of the composition guide 2100 is set too close to the orifice of the nozzle 1500, the refrigerant sprayed from the nozzle 1500 may collide with the composition guide 2100, forming turbulence. Considering the stable spraying of the composition and refrigerant and the deceleration of the refrigerant spray RCC due to turbulence, it is preferable not to form turbulence.

[0296] The output end of the composition guide 2100 can be configured to be spaced apart from the orifice of the nozzle 1500 by a first distance in a direction parallel to the central axis CA of the nozzle 1500, and spaced apart from the orifice of the nozzle 1500 by a second distance in a direction orthogonal to the central axis CA of the nozzle 1500.

[0297] The first distance can be within approximately 20 mm. For example, the first distance can be 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.

[0298] The second distance can be within approximately 10 mm. For example, the second distance can be 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. As mentioned above, reducing the first and second distances allows the composition to be frozen more easily; however, when both are reduced excessively, problems with turbulence formation may occur.

[0299] For example, the composition inflow location can be determined as a position spaced at a predetermined distance from the nozzle 1500 and corresponding to the edge of the main stream S1 of the refrigerant spray RSS formed by the nozzle 1500. In this case, the first distance and the second distance can be determined based on the boundary between the main stream S1 and the branch stream S2 of the refrigerant spray RSS.

[0300] 2.4.3 Implementation of Systems for Cryogenic Spraying

[0301] To realize a hybrid spraying system 100 capable of cryogenic spraying, the refrigerant spray flow temperature, composition flow rate, composition inflow location, or combinations thereof described above may be considered.

[0302] Fundamentally, the hybrid spray system 100 needs to achieve a state where the composition is frozen on the skin surface. To achieve this, the temperature of the refrigerant spray stream RSS formed in the hybrid spray system 100 must be equal to or less than the freezing point (or solidification point) of the composition. Specifically, at the location or area where the composition is introduced, the temperature of the refrigerant spray stream RSS must be equal to or less than the freezing point of the composition. For example, the freezing point of the composition may be from about -30°C to about 0°C. In this case, at the location where the composition is introduced, the temperature of the refrigerant spray stream RSS can be controlled to be equal to or less than about -50°C or about -30°C.

[0303] The mixing spray system 100 needs to achieve a freezing ratio of the composition on the skin surface that is equal to or greater than a target freezing ratio. The target freezing ratio refers to the ratio of the solid composition to the composition reaching the skin surface. Here, the target freezing ratio can be calculated according to the freezing ratio calculation method described above.

[0304] The target freezing ratio can be determined through a freeze-spray experiment. For example, as described below, a range of effective ratios within which the composition exhibits significant penetration can be calculated by conducting a freeze-spray experiment, and the target freezing ratio can be selected within this effective range. For instance, a first experiment described below demonstrates that the composition has a significant penetration effect when the freezing ratio is 17% or 5%, and a second experiment described below demonstrates that the penetration effect increases with increasing freezing ratio; therefore, the target freezing ratio can be set to be equal to or higher than 17%. Alternatively, the target freezing ratio can be set to be equal to or higher than 5%. The target freezing ratio should be set as high as possible, but further consideration may be needed of limiting factors described below (such as prevention of skin damage, prevention of ice film formation, etc.).

[0305] Taking into account the freezing ratio of the composition, the composition supply device 2000 can be designed to have a suitable flow rate of the composition (e.g., a target flow rate). Here, the target flow rate can be the flow rate of the composition to be sprayed within a predetermined time period. The pressure required to be provided by the actuator 2200 can be specified based on the determined target flow rate. Alternatively, the width of the pipe included in the composition guide 2100 or the width of the pipe connected to the composition guide 2100 can be determined based on the determined target flow rate.

[0306] Considering the freezing ratio of the composition, the composition supply device 2000 can be designed to have a suitable target inflow location for the composition. That is, the positional relationship between the refrigerant spraying device 1000 and the composition supply device 2000 can be specified to determine the suitable target inflow location. As described above, the target inflow location can be determined as a position adjacent to the nozzle 1500 and where vortex formation is minimized based on the orifice of the nozzle 1500. The positional relationship between the nozzle 1500 of the refrigerant spraying device 1000 and the composition guide 2100 can be specified depending on the target inflow location. Specifically, based on the orifice of the nozzle 1500, the output end of the composition discharged from the composition guide 2100 can be designed to be located at the target inflow location.

[0307] Considering the freezing ratio of the composition, the refrigerant spraying device 1000 can be designed to ensure the refrigerant has a suitable temperature. For example, when spraying the composition and refrigerant from the mixing spraying system 100, the heating unit 1300 can be controlled such that the calculated freezing ratio is equal to or greater than the target freezing ratio. Specifically, when determining the freezing ratio of the composition in the observation area OR of the refrigerant spray stream RSS while simultaneously using the controller 1900 to change the heat energy per unit time generated by the heating unit 1300, an operating range of the heating unit 1300 can be specified within which the freezing ratio is equal to or greater than the target freezing ratio.

[0308] Here, when the heating unit 1300 is implemented with a thermoelectric element, the operating range may refer to the range of power that needs to be applied to the heating unit 1300. Similarly, here, when the heating unit 1300 is implemented with a thermoelectric element and the controller 1900 applies power to the thermoelectric element using feedback control based on a preset target temperature and the real-time temperature of the skin surface, the operating range may refer to the target temperature range that needs to be set.

[0309] The controller 1900 can control the heating unit 1300, causing the heating unit 1300 to operate within a specified operating range. For example, the controller 1900 can apply power to the heating unit 1300 within a preset power range. The preset power range may refer to a range where the freezing ratio is between 5% and 100%. Alternatively, the preset power range may refer to a range where the freezing ratio is between 17% and 100%. Alternatively, the preset power range may refer to a range where the freezing ratio is between 48% and 100%. Alternatively, the preset power range may refer to a range where the freezing ratio is between 71% and 100%.

[0310] Simultaneously, the operating range of the heating unit 1300 can be specified by further considering the range within which the temperature of the refrigerant spray stream RSS will not cause pain or damage to the skin surface. For example, when the composition and refrigerant are sprayed onto the skin surface from the mixing spray system 100, the operating range of the heating unit 1300 can be determined such that the temperature of the skin surface is equal to or greater than a safe temperature. The safe temperature can be determined in the range of about -10°C to about 20°C. For example, the safe temperature can be -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, or 20°C.

[0311] Furthermore, the operating range of the heating unit 1300 can be specified by further considering the extent to which the refrigerant spray stream RSS will not form an ice film (which is a substance that hinders penetration) on the skin surface. For example, when the composition and refrigerant are sprayed onto the skin surface from the mixing spray system 100, the operating range of the heating unit 1300 can be determined such that the temperature of the skin surface is equal to or greater than the ice film formation temperature. Because an ice film may form when the skin surface temperature is equal to or less than 0°C, the ice film formation temperature is 0°C.

[0312] Simultaneously, the controller 1900 may not operate the heating unit 1300, or the heating unit 1300 may be omitted from the hybrid spraying system 100. Specifically, as the composition at room temperature is introduced into the refrigerant spray stream RSS, the temperature of the refrigerant spray stream RSS may rise. This is because when the introduced composition raises the temperature of the refrigerant spray stream RSS to above the safe temperature and / or ice film formation temperature, not heating the refrigerant before spraying may increase the likelihood of the composition being frozen or the freezing ratio of the composition.

[0313] The refrigerant pressure can be controlled to regulate the temperature of the refrigerant spray stream RSS.

[0314] First, taking into account the freezing ratio of the composition, the internal pressure of the refrigerant container RC used in the mixing spraying system 100 can be appropriately selected. For example, the internal pressure of the refrigerant container RC can be determined in the range of 10 bar to 1000 bar. Preferably, the internal pressure of the refrigerant container RC can be determined in the range of 30 bar to 200 bar.

[0315] The internal pressure of the refrigerant container RC can be determined taking into account the target freezing ratio and the safe temperature. For example, the internal pressure of the refrigerant container RC can be determined to be between a minimum pressure value and a maximum pressure value, at which the freezing ratio of the composition becomes the target freezing ratio, and at which the temperature of the skin surface becomes the safe temperature.

[0316] Meanwhile, the refrigerant pressure can be controlled by the independent compressor described above and / or a container heater that heats the refrigerant container RC. The compressor or container heater can control the refrigerant pressure before spraying within a pressure range determined based on the target refrigeration ratio and safe temperature.

[0317] In the preceding text, when implementing the hybrid spraying system 100 for cryogenic spraying, it has been described that the composition flow rate, the composition inflow location, and the refrigerant spray temperature are considered in sequence. However, the technical concept of this disclosure is not limited thereto, and the hybrid spraying system 100 can be designed such that these factors are considered in different orders.

[0318] Therefore, the proposed hybrid spraying system 100 includes: a refrigerant container RC storing refrigerant at a pressure of at least 30 bar to 200 bar; a refrigerant receiving section receiving refrigerant from the refrigerant container RC; a nozzle 1500 having an orifice of a predetermined size; a composition guide 2100 positioned adjacent to the nozzle 1500, with the output end of the composition guide 2100 located within a predetermined distance from the orifice of the nozzle 1500; a flow regulating unit 1200; and a controller 1900. Here, the freezing ratio of the composition in the observation area OR is equal to or greater than a target freezing ratio, and the observation area OR is positioned at an observation distance OD spaced from the orifice of the nozzle 1500 and has an observation width OW. The hybrid spraying system 100 may further include a distance holding unit, and the length of the distance holding unit is within a recommended spraying distance range to ensure that the freezing ratio of the composition is equal to or greater than the target freezing ratio.

[0319] The above has described a hybrid spraying system 100 that is capable of cryogenic spraying. The hybrid spraying system 100, which is implemented such that at least a portion of the composition is frozen and reaches the skin surface, may also be referred to as a cryogenic spraying system.

[0320] 2.4.4 Spraying composition after freezing

[0321] The hybrid spraying system 100 described above sprays the composition together with a refrigerant, causing the composition to be frozen by the refrigerant during the spraying process. However, a system for cryo-spraying cannot be achieved simply by spraying a mixture of composition and refrigerant; any system can be used for cryo-spraying as long as the frozen composition can reach the skin surface. For example, a system that pre-freezes the composition and then sprays the frozen composition can be used. Specifically, a system that pre-freezes the composition to generate frozen particles and then uses a delivery medium (such as compressed air) to spray the frozen particles onto the skin surface can be used.

[0322] 2.5 Cryogenic Spraying Method

[0323] The following will refer to Figure 12 A cryogenic spraying method using a hybrid spraying system 100 is described.

[0324] Figure 12 A flowchart illustrating a cryogenic spraying method according to one embodiment is provided.

[0325] refer to Figure 12 The cryogenic spraying method includes: preparing a mixing spraying system 100 (S1100); positioning the mixing spraying system 100 based on a target area (S1300); and using the mixing spraying system 100 to spray the composition together with a refrigerant onto the target area (S1500).

[0326] The following section will describe each step in detail.

[0327] First, the user (or operator) can prepare the mixing spray system 100 (S1100). The mixing spray system 100 includes at least: a nozzle 1500 for forming a refrigerant spray stream RSS and a composition guide 2100 disposed adjacent to the nozzle 1500. In addition to the nozzle 1500 and the composition guide 2100, the mixing spray system 100 may also include other components described above.

[0328] Users can locate the hybrid spraying system 100 (S1300) based on the target area.

[0329] For example, the user can position the nozzle 1500 of the hybrid spraying system 100 at a predetermined distance from the target area.

[0330] Here, the predetermined distance can refer to the shortest distance between the orifice of nozzle 1500 and the target area. The predetermined distance can be substantially the same as the recommended spraying distance described above. When the recommended spraying distance is presented in the form of a range, the predetermined distance can be included within the range of the recommended spraying distance.

[0331] Similarly, here, the central axis CA of the nozzle 1500 can have a preset angle relative to the target area. For example, the angle formed between the central axis CA of the nozzle 1500 and the plane including the target area or the virtual plane in contact with the target area can have a value of about 45° to about 90°.

[0332] The user can use the hybrid spraying system 100 to spray the composition together with the refrigerant onto the target area (S1500). For example, when the user operates the input unit 1700 provided in the hybrid spraying system 100, the flow regulating unit 1200 can be turned on and the actuator 2200 can pressurize the composition, causing the refrigerant to be sprayed onto the target area together with the composition. In the case where the hybrid spraying system 100 does not include the actuator 2200, when the user operates the input unit 1700 (e.g., when the user presses the spraying start button), the flow regulating unit 1200 can be turned on to form a refrigerant spray stream RSS, and the composition can be introduced into the refrigerant spray stream RSS and sprayed due to negative pressure.

[0333] When the mixing spray system 100 is in operation, the composition stored in a liquid state is introduced into the refrigerant spray stream RSS. Due to the refrigerant spray stream RSS, the liquid composition is broken into particles, and simultaneously, as its temperature decreases, it transforms into a solid state in the form of frozen particles. The solid composition is accelerated in the acceleration section of the refrigerant spray stream RSS and reaches the target area. Furthermore, when the mixing spray system 100 is viewed from the side at a point in time during operation, an observation area OR can be designated. The observation area OR is spaced from the orifice of the nozzle 1500 by an observation distance OD corresponding to a predetermined distance and has an observation width OW. The freezing ratio in the observation area OR can be 5%.

[0334] 2.6 Confirmation of the penetration effect of cryogenic spraying

[0335] The following section will describe the skin penetration effect of cryo-spray through a cryo-spray experiment.

[0336] 2.6.1 Experiments related to cryogenic spraying

[0337] The applicant conducted several experiments related to cryogenic spraying, including experiments on penetration effects depending on the freezing rate and experiments on penetration effects depending on the freezing ratio.

[0338] First, the first experiment confirming the permeation effect dependent on freezing will be described.

[0339] The purpose of the first experiment was to demonstrate that the permeation effect varies depending on whether the composition is frozen.

[0340] In the first experiment, the penetration effects were compared among the following three conditions: the composition was sprayed onto the skin surface in a non-frozen state (test group 1), the composition was sprayed onto the skin surface in a partially frozen state (test groups 2 and 4), and the composition was sprayed onto the skin surface in a mostly frozen state (test group 3).

[0341] Human skin tissue was used as the target material for the composition. Specifically, facial skin tissue discarded after surgery was used.

[0342] In the control group, human skin tissue was cut to a predetermined size (2cm × 2cm) and the composition was applied to it. The composition contained acetylhexapeptide-8-FITC in combination with a fluorescent substance (fluorescein isothiocyanate, FITC) to demonstrate its penetration effect.

[0343] Then, 24 hours later, fluorescence images of cross-sections of human skin tissue were captured, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0344] In test group 1, human skin tissue was cut to a predetermined size and sprayed with an unfrozen composition. The composition contained an antifreeze agent (PG) to prevent freezing by a refrigerant and acetyl hexapeptide-8-FITC in combination with a fluorescent substance (FITC) to confirm the penetration effect.

[0345] The composition is sprayed using the hybrid spraying system 100 described above. Specifically, the refrigerant spraying device 1000 described above and the composition supply device 2000 according to the second embodiment are used. For the hybrid spraying system 100 used, the freezing ratio is calculated to be 0%.

[0346] Then, 24 hours later, fluorescence images of cross-sections of human skin tissue were captured, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0347] In test group 2, human skin tissue was cut to a predetermined size, and only a portion of the composition was frozen and sprayed onto it. The composition contained acetyl hexapeptide-8-FITC in combination with a fluorescent substance (FITC) to confirm the penetration effect.

[0348] The composition is sprayed using the above-described hybrid spraying system 100. Specifically, the above-described refrigerant spraying device 1000 and the composition supply device 2000 according to the second embodiment are used. For the hybrid spraying system 100 used, the refrigerant ratio is calculated to be 17% (with a measurement error within 5%, i.e., about 12% to about 22%).

[0349] Then, 24 hours later, fluorescence images of cross-sections of human skin tissue were captured, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0350] In test group 3, human skin tissue was cut to a predetermined size, and most of the composition was frozen and sprayed onto it. The composition contained acetyl hexapeptide-8-FITC in combination with a fluorescent substance (FITC) to confirm the penetration effect.

[0351] The composition is sprayed using the hybrid spraying system 100 described above. Specifically, the refrigerant spraying device 1000 described above and the composition supply device 2000 according to the second embodiment are used. For the hybrid spraying system 100 used, the freezing ratio is calculated to be 100% (with a measurement error within 1%, i.e., about 99% to about 100%).

[0352] Then, 24 hours later, fluorescence images of cross-sections of human skin tissue were captured, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0353] In test group 4, human skin tissue was cut to a predetermined size, and only a portion of the composition was frozen and sprayed onto it. The composition contained acetyl hexapeptide-8-FITC in combination with a fluorescent substance (FITC) to confirm the penetration effect.

[0354] The composition is sprayed using the above-described hybrid spraying system 100. Specifically, the above-described refrigerant spraying device 1000 and the composition supply device 2000 according to the first embodiment are used. For the hybrid spraying system 100 used, the refrigerant ratio is calculated to be 5% (with a measurement error within 1%, i.e., about 4% to about 6%).

[0355] Then, 24 hours later, fluorescence images of cross-sections of human skin tissue were captured, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0356] The applicant conducted a second experiment to confirm the permeation effect depending on the freezing ratio.

[0357] The purpose of the second experiment was to confirm that the permeation effect varies depending on the freezing ratio.

[0358] In the second experiment, the composition was sprayed onto the skin surface in a frozen state, and the penetration effect was compared among the following five conditions: a freezing ratio of 5% (measurement error within 1%, i.e., about 4% to about 6%) (test group 1), a freezing ratio of 17% (measurement error within 5%, i.e., about 12% to about 22%) (test group 2), a freezing ratio of 48% (measurement error within 3%, i.e., about 45% to about 51%) (test group 3), a freezing ratio of 71% (measurement error within 3%, i.e., about 68% to about 74%) (test group 4), and a freezing ratio of 100% (measurement error within 1%, i.e., about 99% to about 100%) (test group 5).

[0359] The composition is sprayed using the hybrid spraying system 100 according to the second embodiment.

[0360] The method of adjusting the freezing ratio is to adjust the heat energy applied to the refrigerant before spraying by adjusting the heating unit 1300 of the mixing spraying system 100.

[0361] More specifically, the heating unit 1300 includes a thermoelectric element and the power applied to the thermoelectric element is regulated. As the heat energy applied to the refrigerant before it is sprayed through the nozzle 1500 changes, the temperature of the refrigerant spray stream RSS formed in the nozzle 1500 changes, and the freezing ratio of the composition changes accordingly.

[0362] Here, the applied power is regulated using pulse width modulation (PWM), and the heating power applied using PWM is divided into 0 to 999 levels. From test group 1 to test group 5, the freezing ratio is adjusted by changing the heating power applied to the thermoelectric element.

[0363] In the second experiment, a hydrogel was used as the spraying target for the composition and refrigerant, and the penetration effect was compared by the number of pores formed in the hydrogel. The number of pores formed in the hydrogel was determined visually, and it was determined that the penetration effect was enhanced as the number of pores formed after a predetermined time period of spraying the composition and refrigerant onto the hydrogel increased.

[0364] 2.6.2 Experimental Results and Analysis

[0365] The following will refer to Figures 13 to 16 Describe the results of the first and second experiments.

[0366] Figure 13 and Figure 14 This is a view showing the results of a first experiment used to confirm the permeation effect depending on freezing and the permeation effect depending on the freezing ratio.

[0367] Based on the results of the first experiment, the penetration effect when the composition was sprayed in a frozen state (test group 2 and test group 4) was significantly higher than that when the composition was sprayed in a non-frozen state (test group 1).

[0368] refer to Figure 13 The fluorescence intensity in the control group was 192.04, in test group 1 it was 637.65, in test group 2 it was 2136.44, and in test group 4 it was 1399.54. Understandably, compared to test group 1, the penetration effect in test group 2 was approximately 3.35 times better, and the penetration effect in test group 4 was approximately 2.19 times better.

[0369] Furthermore, when observing fluorescence images of cross-sections of skin tissue under various conditions, such as Figure 14 As shown, it was confirmed that the amount of the composition that permeated in test groups 2 and 4 was significantly increased compared to test group 1.

[0370] Meanwhile, in test group 3, the fluorescence intensity was measured at 429.05, which was lower than that of test group 1. This is because, as mentioned above, the low temperature of the sprayed refrigerant causes an ice film to form on the surface of human skin tissue, and therefore, a large number of frozen particles cannot reach the skin tissue surface. It is expected that no ice film will form in areas with body heat (such as human skin), and therefore, when the conditions of test group 3 are applied to human skin, a higher penetration effect can be expected.

[0371] Figure 15 A view showing the results of a second experiment used to confirm the permeation effect depending on the freezing ratio. Figure 16 A view showing the penetration effect of test group 1 and test group 5 in the second experiment.

[0372] The results of the second experiment confirmed that the penetration effect increased with the increase of the freezing ratio.

[0373] refer to Figure 15 The number of pores was 2 when the freezing ratio was 5%; 5 when the freezing ratio was 17%; 10 when the freezing ratio was 48%; 15 when the freezing ratio was 71%; and 18 when the freezing ratio was 100%. This confirms that the number of pores increases with increasing freezing ratio. Therefore, it is understandable that the permeation effect improves with increasing freezing ratio.

[0374] The penetration effect can also be verified by visual inspection. For example... Figure 16 As shown, the number of pores formed in the hydrogel in test group 5 is significantly increased compared to test group 1.

[0375] Based on the first and second experiments, an effective ratio range for cryogenic spraying can be set. According to the first experiment, the penetration effect of the composition is significant when the cryogenic ratio of the composition is 5% and 17%. Furthermore, according to the second experiment, the penetration effect is improved when the cryogenic ratio of the composition is 17% compared to 5%; the penetration effect is improved when the cryogenic ratio of the composition is 48% compared to 17%; the penetration effect is improved when the cryogenic ratio of the composition is 71% compared to 48%; and the penetration effect is improved when the cryogenic ratio of the composition is 100% compared to 71%.

[0376] Therefore, the effective ratio can range from 5% to 100%. Alternatively, the effective ratio can range from 5% to 17%. Alternatively, the effective ratio can range from 5% to 48%. Alternatively, the effective ratio can range from 5% to 71%. Alternatively, the effective ratio can range from 17% to 48%. Alternatively, the effective ratio can range from 17% to 71%. Alternatively, the effective ratio can range from 17% to 100%. Alternatively, the effective ratio can range from 48% to 71%. Alternatively, the effective ratio can range from 48% to 100%. Alternatively, the effective ratio can range from 71% to 100%.

[0377] Considering the measurement error range, the effective ratio can range from 2% to 100%. Alternatively, the effective ratio range can be from 2% to 22%. Alternatively, the effective ratio range can be from 2% to 51%. Alternatively, the effective ratio range can be from 2% to 74%. Alternatively, the effective ratio range can be from 12% to 51%. Alternatively, the effective ratio range can be from 12% to 74%. Alternatively, the effective ratio range can be from 12% to 100%. Alternatively, the effective ratio range can be from 45% to 74%. Alternatively, the effective ratio range can be from 45% to 100%. Alternatively, the effective ratio range can be from 68% to 100%.

[0378] The mixed spraying system 100 can be designed so that the freezing ratio of the sprayed composition is within the effective ratio range.

[0379] 3. Control of cryogenic spraying characteristics

[0380] The meaning of cryo-spraying, the hybrid spraying system 100 for performing the cryo-spraying method, and the confirmation of the penetration effect through experiments related to cryo-spraying have been described above.

[0381] In cryogenic spraying, the frozen particles of the composition can have the following characteristics: particle size and spraying speed. These characteristics may be important control factors for the commercialization of hybrid spraying systems 100 that perform cryogenic spraying.

[0382] For compositions with specific viscosity and surface tension, the size of the frozen particles can be controlled by the temperature of the refrigerant spray RSS, the flow rate of the refrigerant spray RSS, and the composition flow rate. Additionally, the size of the frozen particles can be controlled by the shape of the output end of the composition guide 2100, where the composition is located when it is about to be introduced into the refrigerant spray RSS. For example, the output end of the composition guide 2100 can be blunt or pointed, and the size of the frozen particles in the blunt output end may be larger than that in the pointed output end.

[0383] 3.1 Control of frozen particle size in cryogenic spraying

[0384] The frozen particles formed from the cryogenic liquid composition have a particle size. As the size of the frozen particles decreases, the mass of the refrigerant in the refrigerant spray RSS increases relative to the mass of the composition, which has an initial velocity of essentially zero immediately after the composition is introduced into the refrigerant spray RSS. This means that, according to the law of conservation of momentum, the velocity of the frozen particles increases as the size of the frozen particles decreases. However, when the size of the frozen particles decreases excessively, the increase in surface area relative to momentum may increase air resistance. Therefore, the deceleration of the spray velocity may increase when the solid composition reaches the skin surface.

[0385] Figure 17 A view illustrating the relationship between particle size and spraying speed according to one embodiment. Figure 17 The frozen particle size shown at each point on the curve refers to the average particle size of at least a portion of the frozen particles of the composition. (Obtained) Figure 17 The graph shown is used when employing the hybrid spraying system 100 according to the second embodiment, and PWM control is used as the method for controlling the size of the frozen particles of the composition. Specifically, as the heating power level applied by the PWM method increases, the size of the frozen particles of the composition decreases.

[0386] refer to Figure 17 It can be seen that as the particle size of the composition decreases, the freezing speed of the composition increases, but when the particle size of the composition decreases to the level equal to or less than the predetermined level, the freezing speed of the composition decreases.

[0387] Therefore, the size of the frozen particles in the composition can be set based on the point where the velocity of the frozen particles is at its maximum. For example, the hybrid spraying system 100 can be designed such that the average size of the frozen particles in the composition is equal to or less than about 60 μm or close to about 20 μm. As another example, when considering the direction of increasing the freezing ratio of the composition, the hybrid spraying system 100 can be designed such that the average size of the frozen particles in the composition is equal to or less than about 150 μm or close to about 70 μm. As yet another example, the hybrid spraying system 100 can be designed such that the average size of the frozen particles in the composition is within the range of about 20 μm to about 60 μm, about 20 μm to about 100 μm, about 10 μm to 60 μm, or about 10 μm to 300 μm.

[0388] In the above text, the average size of the frozen particles refers to the average size of the composition particles frozen in the refrigerant spray stream RSS. However, the method for calculating the average size of the frozen particles in the observation area OA described above can be used as a method for calculating the average size of the frozen particles in the composition.

[0389] Here, the temperature control method for the refrigerant spray stream RSS described above can be used as a method for controlling the size of frozen particles. For example, the size of frozen particles in the composition can be controlled by controlling the degree of heating of the refrigerant by the pre-spray heating unit 1300.

[0390] Meanwhile, if the particle size of the frozen composition (or solid composition) is excessively large, the frozen particles may irritate pain points and cause pain when sprayed onto the skin surface. Specifically, pain may occur when the size of the frozen particles is much larger than the size of skin cells (approximately 30 μm) or the size of pores on the skin surface (approximately 20 μm to approximately 50 μm). Therefore, the hybrid spraying system 100 can be designed such that the size of the frozen particles is less than approximately 20 μm to approximately 50 μm.

[0391] The size of the frozen particles in the composition can be controlled to control the depth of skin penetration of the composition.

[0392] After penetrating the epidermis, the frozen particles melt due to body heat. Because the melting time varies depending on the size of the frozen particles, the melting location of the composition within the skin will also vary. By controlling the size of the frozen particles, the melting location of the composition can be controlled, and the penetration depth of the composition can be controlled accordingly.

[0393] For example, under the same velocity conditions, the penetration depth may increase with increasing frozen particle size and decrease with decreasing frozen particle size. Therefore, after determining the target penetration depth and specifying the range of frozen particle sizes corresponding to the determined penetration depth, at least one of the following can be selectively determined: the heating power level applied to the heating unit 1300 based on the corresponding frozen particle size range, the temperature of the refrigerant container RC, the shape of the output end of the composition guide 2100, the adhesion strength between the composition guide 2100 and the composition, and the composition flow rate.

[0394] Additionally, for compositions unsuitable for penetration into the dermis, such as compositions not belonging to the pharmaceutical or drug category, the size of the frozen particles in the composition can be reduced to limit the penetration depth to the stratum corneum. For example, the mixed spraying system 100 can be designed / controlled such that the size of the frozen particles in the composition is from about 10 μm to about 50 μm.

[0395] 3.2 Control of spraying speed

[0396] The penetration effect may be enhanced as the velocity of the frozen particles increases when the composition reaches the skin surface.

[0397] As a method to increase the speed of freezing particles in the composition, there are methods to reduce the size of the frozen particles. For example, the amount of refrigerant heated before spraying can be increased to reduce the size of the frozen particles. Alternatively, the shape of the end of the composition guide 2100 can be made sharper.

[0398] As a method to increase the speed of the refrigerant particles in the composition, there are methods to increase the spraying speed of the refrigerant particles that transfer kinetic energy to the composition. For example, the spraying speed of the refrigerant particles can be increased by increasing the internal pressure of the refrigerant container RC that stores the refrigerant.

[0399] To increase the velocity of the frozen particles in the composition, the length of the acceleration section described above can be fixed to be equal to or greater than a predetermined level. In other words, the refrigerant and composition can be sprayed onto the skin surface when the nozzle 1500 is spaced from each other by a distance equal to or greater than the minimum acceleration distance. Here, the minimum acceleration distance can be selected in the range of about 3 mm to about 5 mm or about 1 mm to about 10 mm.

[0400] The hybrid spraying system 100 can be designed such that the velocity of the frozen particles of the composition is equal to or greater than 50 m / s. Alternatively, the hybrid spraying system 100 can be designed such that the velocity of the frozen particles of the composition is equal to or greater than 60 m / s, 70 m / s, 80 m / s, 90 m / s, 100 m / s, 110 m / s, or 120 m / s. Here, the velocity of the frozen particles of the composition can refer to the average velocity of the particles of the composition moving in the refrigerant spray stream RSS. For example, the velocity of the frozen particles of the composition can be obtained by tracking each frozen particle in an image captured by a high-speed camera, measuring the velocity, and calculating the average value. Here, the velocity of the frozen particles can be calculated as the average velocity of at least a portion of the particles in the refrigerant spray stream RSS. Alternatively, the velocity of the frozen particles can be calculated as the average velocity of the particles in the observation area OR as described above.

[0401] Simultaneously, by increasing the spraying speed of the composition, it is possible to prevent the composition from slowing down due to air resistance until it reaches the skin surface. For example, the formation of a sheath jet around the refrigerant spray stream RSS can prevent the composition particles from contacting the air. To form the sheath jet, the mixing spraying system 100 may further include a sheath nozzle. The sheath nozzle can spray refrigerant or compressed air to surround the refrigerant spray stream RSS. The sheath nozzle is disposed around the nozzle 1500 and may have an annular spray orifice. Alternatively, the sheath nozzle may consist of a plurality of nozzles arranged around the nozzle 1500. When the temperature of the sheath jet is equal to or less than a predetermined level (e.g., the freezing point of the composition), it is possible to prevent the temperature of the composition freezing particles from decreasing.

[0402] 4. Temperature control of the target area

[0403] In methods where the refrigerant is sprayed together with the composition, the temperature or pressure of the refrigerant, and the skin surface temperature due to the refrigerant, can significantly affect the composition's ability to penetrate the skin. For example, as described above, the temperature or pressure of the refrigerant may contribute to freezing the composition and causing it to impact the skin in a solid state.

[0404] Furthermore, regardless of whether the composition is frozen, the temperature of the skin surface can affect its permeability. For example, when the skin surface temperature decreases, the stratum corneum of the epidermis hardens, thus potentially shortening the impact time and increasing the impact force, making the composition easier to penetrate. Conversely, as mentioned above, when the skin surface temperature drops excessively, an ice film may form on the skin surface or an ice layer may form inside the skin, making it difficult for the composition to penetrate.

[0405] Therefore, the applicant conducted experiments to demonstrate how the penetration effect of the composition varies depending on the temperature of the skin surface.

[0406] 4.1 Methods for controlling skin surface temperature

[0407] The temperature of the skin surface to which the refrigerant and composition are sprayed can be controlled by the above-described mixing spraying system 100. For example, when the refrigerant and composition are sprayed onto the skin surface by the mixing spraying system 100, the controller 1900 can acquire the real-time temperature of the skin surface as measured in real time by the sensor unit 1600; use a PID control method to acquire the power to be applied to the heating unit 1300, the PID control method taking the difference between the preset target temperature and the real-time temperature as the input value and the power to be applied to the heating unit 1300 as the output value; and heat the refrigerant before spraying by applying the acquired power to the heating unit 1300 to maintain the temperature of the skin surface at the target temperature.

[0408] For example, the temperature of the skin surface can be maintained at -10℃, -9℃, -8℃, -7℃, -6℃, -5℃, -4℃, -3℃, -2℃, -1℃, 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, 11℃, 12℃, 13℃, 14℃, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, or 25℃. Here, maintaining the temperature of the skin surface at a specific temperature means that the temperature measured on the skin surface within a predetermined time period is within the error range of that specific temperature (e.g., -1℃ to +1℃).

[0409] 4.2 Experiments used to determine the degree of penetration that depends on the temperature of the skin surface

[0410] The following will refer to Figure 18 Experiments for observing the permeability of the composition depending on the temperature of the skin surface are described, and the appropriate skin surface temperature is described with reference to the experimental data.

[0411] The experimental procedure is as follows:

[0412] Rabbits were used as experimental animals. After general anesthesia, the skin on the back of the rabbits was shaved and divided into 10 areas (3cm × 3cm). The composition and refrigerant were sprayed using the mixed spraying system 100 according to the first embodiment.

[0413] FITC-glucan (3 kDA to 5 kDA) was used as a composition in which FITC (i.e., fluorescent labeling substance) was linked to glucan.

[0414] Subsequently, tissue samples were collected and stained with DAPI, and the fluorescence intensity in the tissue samples was measured using a fluorescence microscope.

[0415] The experimental subjects included an untreated group and three experimental groups (numbers 1-3). In the untreated group, FITC-glucan was applied to the rabbit skin. In the first experimental group, FITC-glucan was sprayed onto the rabbit skin while maintaining a skin temperature of -3°C. In the second experimental group, FITC-glucan was sprayed onto the rabbit skin while maintaining a skin temperature of 0°C. In the third experimental group, FITC-glucan was sprayed onto the rabbit skin while maintaining a skin temperature of 3°C.

[0416] Figure 18 A view showing the results of an experiment used to demonstrate the penetration effect that depends on skin surface temperature. Figure 18 (a) shows the fluorescence intensity of each experimental group, and Figure 18 (b) shows the permeability of each experimental group.

[0417] refer to Figure 18 The penetration ability of the refrigerant mixed with the composition and sprayed is higher than that of the composition alone. Furthermore, during the spraying process of the refrigerant and composition, the penetration ability is highest when the skin surface temperature is maintained at 3°C, and the penetration ability is higher when the skin surface temperature is maintained at -3°C than when the skin surface temperature is maintained at 0°C.

[0418] Therefore, it is understandable that the penetration ability is greatly enhanced when the sprayed refrigerant and composition are applied while the skin surface temperature is maintained at about 3°C.

[0419] As demonstrated in the experiments above, the permeability of the composition is enhanced when the skin surface temperature is maintained at a specific temperature. Therefore, as will be discussed later, it is necessary to determine the permeability of the composition while controlling the target temperature of the skin surface, and to find the target temperature at which the permeability of the composition exceeds a predetermined level.

[0420] 4.3 Method for determining the target temperature

[0421] The following section describes a prediction example used to determine the target temperature that the skin surface temperature should be maintained at.

[0422] The third experiment was conducted as follows.

[0423] Prepare a mixing spraying system 100. Here, as described above, the mixing spraying system 100 includes a refrigerant spraying device 1000 that generates a refrigerant spray stream RSS, and a composition supply device 2000 connected thereto and enabling the composition to be introduced into the refrigerant spray stream RSS. The internal pressure of the refrigerant container RC storing the refrigerant is 50 bar, and carbon dioxide is used as the refrigerant.

[0424] The refrigerant spraying device 1000 of the hybrid spraying system 100 includes a thermoelectric element for applying heat to the refrigerant and employs a PID control method that provides power to the thermoelectric element based on the real-time temperature obtained by measuring the temperature of the target area.

[0425] Rabbits were used as experimental animals. After general anesthesia, the skin on the back of the rabbits was shaved and divided into 10 areas (3cm × 3cm). The composition and refrigerant were sprayed using a mixed spraying system 100. Here, the target temperature of the rabbit skin surface was set to 0°C.

[0426] FITC-glucan (3 kDA to 5 kDA) was used as a composition in which FITC (i.e., fluorescent labeling substance) was linked to glucan.

[0427] After spraying the composition and refrigerant, tissue samples were collected and stained with DAPI, and the fluorescence intensity in the tissue samples was measured using a fluorescence microscope.

[0428] The target temperature of the skin surface was changed to -10℃, -9℃, -8℃, -7℃, -6℃, -5℃, -4℃, -3℃, -2℃, -1℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, 11℃, 12℃, 13℃, 14℃, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, and 25℃, and the fluorescence intensity (penetration) in the tissue samples at each target temperature was measured.

[0429] Find the threshold temperature range when the fluorescence intensity is equal to or greater than a predetermined level.

[0430] When a hybrid spraying system 100 is realized in the future, the target temperature can be set within the threshold temperature range.

[0431] The fourth experiment was conducted as follows.

[0432] Prepare a mixing spraying system 100. Here, as described above, the mixing spraying system 100 includes a refrigerant spraying device 1000 that generates a refrigerant spray stream RSS, and a composition supply device 2000 connected thereto and enabling the composition to be introduced into the refrigerant spray stream RSS. The internal pressure of the refrigerant container RC storing the refrigerant is 50 bar, and carbon dioxide is used as the refrigerant.

[0433] The refrigerant spraying device 1000 of the hybrid spraying system 100 includes a thermoelectric element for applying heat to the refrigerant. During the spraying of the refrigerant, the refrigerant spraying device 1000 is controlled by applying a constant voltage (e.g., 1 V) to the thermoelectric element.

[0434] Rabbits were used as experimental animals. After general anesthesia, the skin on the back of the rabbits was shaved and divided into 10 areas (3 cm × 3 cm). The composition and refrigerant were sprayed using a mixed spraying system 100.

[0435] FITC-glucan (3 kDA to 5 kDA) was used as a composition in which FITC (i.e., fluorescent labeling substance) was linked to glucan.

[0436] After spraying the composition and refrigerant, tissue samples were collected and stained with DAPI, and the fluorescence intensity in the tissue samples was measured using a fluorescence microscope.

[0437] The voltage applied to the thermoelectric element was changed from 0 V to 5 V in 0.1 V increments, and the fluorescence intensity was measured at each applied voltage.

[0438] Find the threshold voltage range when the fluorescence intensity is equal to or greater than a predetermined level.

[0439] When the hybrid spraying system 100 is realized in the future, the voltage applied to the thermoelectric element can be set within the threshold voltage range.

[0440] The features, structures, effects, etc., described in the implementation schemes are included in at least one implementation scheme of this disclosure and are not necessarily limited to one implementation scheme. Furthermore, those skilled in the art can combine or modify the features, structures, effects, etc., provided in various implementation schemes in other implementation schemes. Therefore, content related to combinations and modifications should be interpreted as being included within the scope of this disclosure.

[0441] The embodiments described herein are provided for illustrative purposes only, and those skilled in the art will understand that various modifications, additions, and substitutions can be made without departing from the scope and spirit of this disclosure. In other words, each element specifically shown in the embodiments can be implemented in modified forms. Therefore, anything relating to combinations and modifications should be interpreted as including within the scope of this disclosure, as disclosed in the appended claims.

[0442] Implementation of the invention

Claims

1. A method for freezing and spraying a composition, the method comprising: Prepare a hybrid spraying system configured to spray a refrigerant and the composition, the hybrid spraying system including a nozzle configured to spray the refrigerant and a composition guide arranged adjacent to the nozzle; The hybrid spraying system is positioned at a certain distance from the target area, wherein the nozzle of the hybrid spraying system has an orifice that is an outlet for spraying refrigerant, and the orifice is positioned facing the target area. By using the hybrid spraying system, the composition containing the refrigerant is sprayed onto the target area. The nozzle forms a refrigerant spray stream, the composition guide directs the liquid composition into the refrigerant spray stream, and a portion of the liquid composition is frozen and arrives at the target area as a solid composition. At a certain point in time during the spraying of the refrigerant and the composition through the mixing spraying system, the freezing ratio in the observation area is greater than or equal to 5%, where the freezing ratio represents the ratio of the composition in its solid state to the composition in its liquid state and the composition in its solid state. The observation area is defined as a region of arbitrary width located at a certain observation distance from the orifice of the nozzle in a side view of the hybrid spraying system. The observation distance refers to the distance between the orifice of the nozzle and the target area.

2. The method of freezing and spraying composition according to claim 1, wherein, In the side view of the hybrid spraying system, the observation area is defined by a first line and a second line. The first line is at the observation distance from the orifice of the nozzle and is perpendicular to the central axis of the nozzle. The second line is at an arbitrary distance from the first line and is parallel to the first line.

3. The method of the freezing and spraying composition according to claim 1, wherein the observation area is within a recommended spraying distance determined for the hybrid spraying system.

4. The method of freezing and spraying composition according to claim 1, wherein, In the observation area at the specified time point, the freezing ratio is the ratio of the number of particles in the solid state of the composition to the sum of the number of particles in the liquid state and the number of particles in the solid state of the composition.

5. The method of freezing and spraying composition according to claim 1, wherein the freezing ratio is 17% or greater.

6. The method of freezing and spraying composition according to claim 1, wherein the velocity of the composition in its solid state reaching the target area is 50 m / s or greater.

7. The method of freezing and spraying composition according to claim 1, wherein the average size of the composition in solid state present in the observation area is 20 μm to 60 μm.

8. A cryogenic spraying system for freezing and spraying compositions, the cryogenic spraying system comprising: A refrigerant container in which refrigerant is stored at a pressure between 10 bar and 1000 bar; A refrigerant receiving unit configured to receive the refrigerant from the refrigerant container; A nozzle having an orifice of a predetermined size and configured to spray the refrigerant, the nozzle pressurizing the refrigerant passing through it, causing the refrigerant passing through the nozzle to encounter atmospheric pressure and expand, thereby lowering the temperature of the refrigerant; A container for containing the composition; A composition guide fluidly connected to the composition container and configured to discharge the composition, the end of the composition guide being arranged adjacent to the nozzle such that the composition is introduced into a stream of refrigerant sprayed by the nozzle; A valve is disposed between the refrigerant receiving unit and the nozzle and is configured to control the flow rate of the refrigerant from the refrigerant receiving unit to the nozzle; and A controller, configured to control the valve, When the refrigerant and the composition are sprayed from the cryogenic spraying system, the freezing ratio at a time point in the observation area is greater than or equal to 5%, where the freezing ratio represents the ratio of the composition in its solid state to the composition in its liquid state. The observation area is positioned at a certain observation distance from the orifice of the nozzle and has an arbitrary width.

9. The cryogenic spraying system according to claim 8, wherein, In a side view of the hybrid spraying system, the observation area is defined by a first line and a second line. The first line is at the observation distance from the orifice of the nozzle and is perpendicular to the central axis of the nozzle. The second line is at an arbitrary distance from the first line and is parallel to the first line.

10. The cryogenic spraying system of claim 8, wherein the observation area is within a recommended spraying distance determined for the hybrid spraying system.

11. The cryogenic spraying system according to claim 8, further comprising: A heating unit is disposed between the refrigerant receiving unit and the nozzle and is configured to heat at least a portion of the refrigerant moving from the refrigerant receiving unit to the nozzle. In this configuration, by using the heating unit, the controller is configured to heat the refrigerant, such that the refrigeration ratio becomes 5% or greater.

12. The cryogenic spraying system according to claim 11, The controller is configured to apply electrical power within a predetermined range to the heating unit. The heating unit is subjected to the electrical power and generates heat energy that is transferred to the refrigerant. The predetermined power range is set such that the freezing ratio becomes 5% or greater.

13. The cryogenic spraying system according to claim 8, wherein, In the observation area at the specified time point, the freezing ratio is the ratio of the number of particles in the solid state of the composition to the sum of the number of particles in the liquid state and the number of particles in the solid state of the composition.

14. The cryogenic spraying system according to claim 8, further comprising: An actuator, coupled to the composition container and configured to supply the composition to the composition guide.

15. The cryogenic spraying system according to claim 8, The composition guide includes an input for the composition to flow into and an output for the composition to discharge out. The output end of the composition guide is positioned at a predetermined distance from the end of the nozzle.

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